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(Hypertension. 2001;37:767.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Workshop: Hypertension and Cardiovascular Risk Factors

Role of the Angiotensin II–Nitric Oxide Interaction

Leopoldo Raij

From the Department of Veterans Affairs Medical Center, Minneapolis, Minn

Correspondence to Leopoldo Raij, MD, Chief, Nephrology/Hypertension Section (111J), Department of Veterans Affairs Medical Center, One Veterans Dr, Minneapolis, MN 55417. E-mail raijx001{at}tc.umn.edu


*    Abstract
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 *Abstract
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Vascular upregulation of nitric oxide (NO) is an adaptive response to increased blood pressure that may help in the prevention of end-organ damage. Differences in cardiovascular and renal morbidity and mortality in hypertensive patients may result, at least in part, from individual variations in endothelial function in response to the hemodynamic workload of hypertension. A functional feedback balance exists between both angiotensin (Ang) II and NO under normal conditions. The NO-Ang II imbalance may not explain all the vascular pathophysiology of hypertension, but it certainly appears to be an important component. In hypertension, salt sensitivity, whether primary (ie, certain populations in the United States and Japan) or secondary (ie, aging, type II diabetes), appears to be a marker of increased cardiovascular and renal risk that is often linked to a decreased bioactivity of NO. In diabetes and atherosclerosis, NO-dependent vascular relaxation is impaired and can be restored by decreasing the synthesis and/or blocking the action of Ang II. An understanding of the relations between hypertension, cardiovascular risk factors, end-organ damage, and the NO-Ang II axis leads one to believe that the combination of therapeutic agents capable of reinstating the homeostatic balance of these vasoactive molecules within the vessel wall would be most effective in preventing or arresting end-organ disease.


Key Words: endothelium • angiotensin II • nitric oxide • stress


*    Introduction
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 up arrowAbstract
 *Introduction
down arrowInteraction of Ang II...
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The role of the renin-angiotensin (Ang) II system, particularly of Ang II, holds high interest in the areas of cardiovascular and renal physiology and pathology. Of most interest, after the discovery of the beneficial effects of Ang II–converting enzyme (ACE) inhibitors in hypertension and cardiovascular and renal disease, are Ang II’s nonhemodynamic effects1 2 rather than its better-known hemodynamic effect as a vasopeptide. The L-arginine/nitric oxide (NO) pathway, particularly NO as an endothelial-derived relaxing factor, has also been an area of keen interest.3 4 5 6 The interactions of and balance between Ang II and NO are of key importance in cardiovascular and renal injury and are the focus of this review. Indeed, the presence or the relative bioavailability of either one can make it either injurious or protective of target organs (Figure 1).



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  		Figure 1. Schematic representation of the pathophysiology of the interaction between Ang II and NO (modified from Reference 72).

Research shows general agreement that functionally complete local renin-angiotensin systems are operative within organs/tissues.7 8 9 The systems act in both autocrine and paracrine fashion,7 8 potentially accounting for the local actions of Ang II and NO; angiotensin II and NO interact at the level of the endothelium, which is where they undergo the final step of synthesis as well as at the level of vascular smooth muscle cells, mesangial cells, and matrix. The endothelial cells contain ACE, which converts Ang I to Ang II. NO has been shown to downregulate the synthesis of ACE10 in the endothelium, as well as Ang II type 1 receptors (AT1) in vascular smooth muscle cells, thus having the potential to decrease Ang II production and action.11 12

NO is synthesized in the endothelium by a constitutive endothelial NO synthetase (eNOS), part of the NOS isoforms family.3 5 eNOS is calcium- and calmodulin-dependent3 5 and can be activated by neurohumoral substances such as acetylcholine, substance P, bradykinin, and adenosine diphosphate as well as by such mechanical stimuli physical forces as shear stress and cyclic strain. Under physiological conditions such as exercise, eNOS is upregulated, leading to vasodilation and increased blood flow to the organs.13 14

NO, which has a short half-life, is rapidly inactivated either by superoxide anions (O2-) or by binding to hemoglobin5 after release. Thus, increased levels of O2-, as they occur in pathological conditions, may dramatically shorten the bioactivity of NO and/or transform it into a toxic metabolite.15 NO actions can be inhibited by NOS inhibitors, whereas Ang II, because it combines with receptors to exert its actions, can be inhibited by Ang II receptor blockers.1 ACE inhibitors not only decrease Ang II synthesis but prevent the degradation of bradykinin, one of the most important physiological molecules involved in the release of NO.16 17 18

The main subtypes of Ang II receptors are AT1 and AT2.19 20 AT1 mediates the vasoconstrictor effect of Ang II and mediates the Ang II–induced growth in cardiovascular and renal tissue.17 NO can downregulate AT1 receptors in vascular tissue11 and the adrenal gland12 and mitigate the actions of Ang II.21 AT2 actions are less well understood, although it is known that in adult animals, they may upregulate in response to injury. AT2 receptors have been associated with the synthesis and/or the release of both prostaglandins and NO.22 23


*    Interaction of Ang II and NO in the Regulation of Vascular Tone
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Hypertension involves 3 major factors: abnormal vascular tone, abnormalities in volume and salt regulation, and vessel wall remodeling. Both NO and Ang II are important players in these pathogenetic mechanisms.

Ang II is a potent vasoconstrictor with growth-promoting properties. In the kidney, this vasoconstrictor effect is more pronounced in the efferent than the afferent glomerular arterioles and leads to an increase in glomerular capillary pressure.24 25 26 Various factors may cause the differential intrarenal vasoconstrictor response to Ang II: smaller efferent arteriolar diameter,27 maintenance of an afferent vasodilatory tone by NO,24 28 29 and activation of AT2 receptors in the afferent arterioles, resulting in vasodilation through the cytochrome P-450–dependent pathway.30

NO is a vasodilator with antigrowth and antithrombogenic effects that plays a role in maintaining vascular integrity and preventing end-organ damage. Its vasodilatory effect is mainly on the afferent arteriole in the cortical nephrons, but it can affect both afferent and efferent arterioles in juxtamedullary nephrons.31 32 AT1 receptor blockade can abolish the vasoconstrictor effect of NOS inhibition on cortical blood flow but has minor effects on medullary blood flow,33 which suggests that NO may be a more effective modulator of Ang II–mediated vasoconstriction in cortical than in medullary nephrons.33 NO production is continuous, imparting a constant vasodilatory effect24 and helping maintain resting vascular tone and normal blood pressure. Ang II production is not as constant, however, and its main physiological role is to increase vascular tone in response to decreased blood volume and/or flow. Its contribution to the steady state of vascular tone in the stable, homeostatic individual is unclear.24 34

The kidney’s inability to adequately excrete salt is considered to be a major pathogenetic component in hypertension. NO may play a role in salt excretion by directly decreasing tubular sodium reabsorption or indirectly through modulation of renal medullary blood flow.15 34 35 36 Ang II, however, has antinatriuretic properties because of its effects on the renal tubules and renal blood flow plus the feedback regulation of renin release from the macula densa.25 34

In people with essential hypertension, impairment of NO-mediated endothelium-dependent relaxation occurs.37 38 At times, the impairment precedes the hypertension, which has been found to occur in some normotensive blacks39 and normotensive offspring of hypertensives.40 Many normotensive offspring of patients with premature myocardial infarction manifest abnormal endothelium-dependent relaxation and increased intima-media thickness in the carotid arteries.41

Development of hypertension has been documented in animals with long-term blockade of NO synthesis or knockout of the NOS gene, whereas hypotension has been found in mice that overexpress the NOS gene.42 43 Local administration of the NOS inhibitor NG-monomethyl-L-arginine into the brachial artery of humans produces a dose-dependent fall in forearm flow,44 which suggests that NO also participates in the regulation of vascular tone in humans.

The synthesis or release of such vasoactive agents as endothelin-1 (ET-1) and Ang II are likely modulated by the effects of NO, as shown by increasing evidence.45 46 Interaction between NO and ET-1 appears to be more important under pathological than physiological conditions, because ET-1 synthesis is upregulated by Ang II and downregulated by NO.

The development and/or maintenance of both hypertension and the abnormal vascular remodeling that occurs in such circumstances as atherosclerosis and after myocardial injury47 48 is probably due in part to a loss of NO and, more important, to an imbalance among Ang II, NO, and O2- production.45 47 49


*    NO-Ang II in Cardiovascular and Renal Injury
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Vascular remodeling is a dynamic process of adaptation of the vascular beds to hypertension caused increases in hemodynamic workload.47 All cellular components participate in the process. In the heart, remodeling results in myocyte hypertrophy and increased extracellular matrix;47 in vessels, it is characterized by an increased media/lumen ratio; and in the glomerulus, it results in an increase in size and number of mesangial cells and/or the amount of mesangial matrix.45 50 51 These adaptive changes end up being maladaptive in many patients, leading to left ventricular hypertrophy (LVH) and heart failure, ischemia of vascular territories, and renal failure.52

Ang II affects growth-related processes directly as well as indirectly by means of synthesis of growth factors such as platelet-derived growth factor and transforming growth factor-ß (TGF-ß).47 51 In addition, it promotes synthesis of ET-1, which is in itself a vasoconstrictor and facilitator of vascular smooth muscle cell and mesangial cell growth.46 53 NO, however, downregulates TGF-ß and has been shown to be a powerful endogenous inhibitor of growth-related responses in vascular smooth muscle cells, mesangial cells, and extracellular matrix.26 In addition, platelet aggregation and the expression of adhesion molecules are inhibited by NO.6 26 These actions of NO have been confirmed in in vivo studies in mice that are genetically deficient in endothelial NOS and subjected to hemodynamic injury.48 54 55 Finally, recent studies have shown that NO downregulates synthesis of both ACE10 and AT1 receptors11 and inhibits the synthesis of ET-1.56 Experimentally, inhibition of renal NO synthesis results in increased intrarenal synthesis of Ang II.57 Clinically, blockade of the AT1 receptor normalizes NO-mediated vascular relaxations in patients with atherosclerosis.58

A new mechanism involved in the countervailing interaction between NO and Ang II was elucidated recently, namely the activation of NADH/NADPH oxidases that lead to the production of O2-. Ang II–driven O2- production has been identified in vascular smooth muscle cells,19 mesangial cells,59 and aortic adventitial fibroblasts.60 Extracellularly, O2- inactivates NO; whereas intracellularly, it activates MAP kinases and leads to vascular smooth muscle and mesangial cell hypertrophy.15 19 59

The pathogenesis of hypertensive end-organ injury is affected by both an NO deficit and an Ang II increase.19 Most studies suggest that end-organ damage in hypertension is diffuse and affects organs to different degrees within individual patients.52 The endothelial response to hypertension is to organize a complex local environment that includes upregulation of NO and inhibition of the effects of Ang II. It is through this endothelial function that end organs may be spared from the effects of hypertension.13 15 61 62

In experimental models of hypertension, spontaneously hypertensive rats (SHR) show increased production of renal, aortic, and cardiac NO, whereas Dahl salt-sensitive rats (DS) show decreased NO production. DS show 5 times more proteinuria than SHR and 9 times more glomerular injury at similar blood pressure;62 63 they also show more aortic hypertrophy and LVH.62 These results suggest that in response to hypertension, DS have a paradoxical decrease in NO production that ultimately promotes cardiovascular and renal injury.62

It is reasonable to conclude that the cause of end-organ dysfunction in hypertensive individuals is multifactorial and that both Ang II and NO appear to play a pivotal but not exclusive role.26 Decreased vascular NO bioactivity that results from endothelial dysfunction may promote abnormal end-organ vascular remodeling through either absolute or relative changes in the level of activity of NO compared with Ang II.26 48


*    NO-Ang II in Diabetes and in Insulin Resistance
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Hypertensive patients as well as their first-degree relatives commonly show abnormalities of insulin, glucose, and lipoprotein metabolism.64 In many patients, insulin resistance, manifested by a defect in the ability of insulin to stimulate the metabolism of glucose by muscle and its storage as glycogen, is the hallmark of this metabolic syndrome. It is important to realize, however, that although insulin resistance and hyperinsulinemia are common in hypertensive patients, hypertension does not occur in all patients with hyperinsulinemia.

Insulin resistance and hyperinsulinemia are more severe and more closely associated with hypertension in obese than in nonobese patients.64 The prevalence of microalbuminuria is increased in hypertensive patients with insulin resistance; microalbuminuria as well as insulin resistance and hyperinsulinemia have been associated with an increased risk for atherosclerotic cardiovascular disease.64

Steinberg et al65 demonstrated that insulin enhances the release of endothelium-derived NO, and Baron et al66 demonstrated that insulin-resistant states including obesity, hypertension, and type 2 diabetes mellitus exhibit blunted insulin-mediated vasodilation and impaired endothelium-dependent vasodilation. These investigators suggested that endothelial dysfunction is an integral component of the syndrome of insulin resistance, independent of hyperglycemia; they further suggested that the endothelial dysfunction worsens insulin resistance and predisposes individuals to macrovascular disease.


*    NO-Ang II in Salt Sensitivity
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Bigazzi et al64 reported that salt-sensitive patients with essential hypertension are more likely to manifest hyperinsulinemia, hyperlipidemia, and microalbuminuria. In this context, therefore, salt sensitivity can be a marker for increased cardiovascular risk in patients with essential hypertension.

Findings by Reaven et al67 demonstrated remarkable similarity between DS and salt-sensitive humans: compared with control Sprague-Dawley rats, DS manifested a defect in insulin-stimulated glucose uptake by isolated adipocytes. These metabolic changes do not depend on DS eating a high-salt diet and do not vary as a function of salt intake, which suggests that in the rats, as in salt-sensitive humans,68 susceptibility to the development of endothelial dysfunction and end-organ disease is part of the cluster of abnormalities that predispose to hypertension.69 Similar to the observations in SHR,62 groups of patients with severe hypertension have been identified who are not salt sensitive, have minimal LVH, no renal injury, and normal endothelial function.70

The association between microalbuminuria and the progression of diabetic nephropathy has been clearly established in patients with type 1 diabetes mellitus. However, recent studies from several laboratories have established that microalbuminuria is a marker of cardiovascular morbidity in nondiabetic patients with essential hypertension as well as in patients with type 2 diabetes mellitus.71 Salt-sensitive hypertensive patients have a greater incidence of microalbuminuria;64 71 72 this has led investigators to suggest that microalbuminuria may be a useful predictor of salt sensitivity and renal hemodynamic abnormalities in patients with essential hypertension.73 In atherosclerosis, there is upregulation of vascular ACE and AT1 receptors and decreased bioactivity of NO. Clinically, AT1 receptor blockade normalizes endothelium-dependent relaxations mediated by NO in patients with atherosclerosis.58 Statins have been shown to upregulate eNOS and decrease ET-1 synthesis.74

The association between endothelial dysfunction, dysregulation of NOS activity, end-organ damage, and salt sensitivity in hypertension is intriguing. Salt-sensitive hypertension has been linked to a decrease in renal NO production, inappropriate activation of the renin-angiotensin system, or both.71 72 However, a causality relationship between salt sensitivity and NO deficiency has not yet been clearly identified.71

Heimann et al75 reported a higher incidence of left ventricular mass in salt-sensitive hypertensive patients than in salt-resistant hypertensive patients. More recently, in a study of 350 Japanese patients with essential hypertension, Morimoto et al76 demonstrated that patients who were salt-sensitive more often had LVH and experienced more cardiovascular events than the non–salt-sensitive hypertensive patients.

Several studies have shown an association between endothelial function and vascular compliance and suggest that endothelium dependent vascular relaxation (EDR) mediated by NO contribute to the maintenance of vascular compliance.77 In the aorta, a reduction in vascular compliance promotes LVH because of increased impedance to left ventricular function.77 It has been reported that salt-sensitive hypertensive patients manifest impaired EDRs that are mediated by NO.68 It has been suggested that impaired vascular relaxation precedes hypertension in some populations of blacks and that it further deteriorates with age and after the development of hypertension.78 Similar observations have been made in Italy in children of hypertensives.40

Impaired NOS activity in salt-sensitive experimental models of hypertension has been demonstrated.62 79 In hypertensive humans, independent of the effects of salt on blood pressure, salt sensitivity may be a marker for susceptibility to cardiovascular and renovascular injury.64 72 It is interesting to note that aging as well as diabetes are characterized by increased prevalence of hypertension, salt sensitivity, and decreased EDR-mediated by NO.68 80 Hence, it is tempting to speculate that in hypertension, salt sensitivity, whether primary (ie, certain populations in the United States and Japan)76 78 or secondary (ie, aging, type II diabetes mellitus),81 is a marker of increased cardiovascular and renal risk that is linked to a decreased bioactivity of NO (Figure 2).



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  		Figure 2. Schematic representation of the relationship between hypertension, end-organ injury, salt sensitivity, and the NO-Ang II interaction (based on References 13, 26, 37–41, 45, 48, 57, 64, 66, 70, 72, 81).


*    NO-Ang II and the Kidney
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NO synthesis inhibition and Ang II stimulation are quite similar in terms of regulation of vascular tone and vascular pathology. It remains unclear the extent to which the vasoconstrictor response to NO blockade results from withdrawal of an active NO vasodilatory stimulus and how closely related this response is to amplification of underlying vasoconstrictor systems.10 82 83

Ang II blockade has not been found to have an effect on the renovasoconstrictor response to acute NO inhibition in the conscious unstressed rat.84 85 In the conscious rat and dog, however, infusion of Ang II given alone at a dose that has little effect on renovascular resistance causes massive renal vasoconstriction when the NO system is also acutely inhibited.86

Thus, the renal vasoconstriction produced by acute NO blockade does not require the participation of the Ang II system. However, when Ang II levels are sufficiently high to affect renovascular tone, NO is important in maintaining renal perfusion.6 24 Intrarenal inhibition of NO causes an increase in afferent arteriolar resistance and a decrease in the ultrafiltration coefficient.87 This is, at least in part, the result of the unopposed action of Ang II.32 88 However, the glomerular capillary pressure does not change unless the systemic administration of NOS inhibitors results in a significant increase in systemic arterial blood pressure.32 88 Selective inhibition of NO synthesis in renal medullary interstitium decreases papillary blood flow and diminishes urinary sodium excretion without altering GFR or systemic blood pressure.89 90

The situation with chronic NOS inhibition is different. Hypertension caused by chronic inhibition is not entirely NO-dependent.91 Moreover, the rescue administration of L-arginine had no effect in a chronic model of hypertension in which NO had been inhibited for 5 to 6 weeks.91 This chronic NO inhibition is accompanied by increased intrarenal Ang II synthesis and upregulation of TGF-ß and results in glomerular and tubulointerstitial injury,62 as well as coronary vascular remodeling, LVH, and hypertension.6 61 Studies that compared endothelial NOS knockout mice to wild mice showed that in the former mice, a more marked increase in vessel wall thickness develops because of vascular smooth muscle hyperplasia in response to hemodynamically mediated vascular injury.48 Pulmonary artery hypertrophy in response to hypoxia is also more marked in these mice.54

Hayakawa and Raij62 suggested that deficiency in NO synthesis conditions the severity of vascular and ventricular hypertrophy in response to hemodynamic changes in genetic models of hypertension. This led to the conclusion that although acute inhibition of NO leads to hypertension, once the chronic phase is established, NO deficiency is not the sole mechanism for the maintenance of hypertension and target organ injury. It has also been suggested that in chronic hypertension, Ang II and ET-1 play an important role in the maintenance of hypertension and cardiorenal damage when NO bioactivity is deficient.46 57 92

In chronic hypertensive models, the administration of ACE inhibitors as well as AT1 blockers reduces the severity of hypertension and ameliorates cardiorenal injury.92 93 AT1 blockers can largely attenuate renal pressor response to NOS inhibition but not to the same degree as the systemic pressor response, suggesting that Ang II may not have a major interaction with NO in the maintenance of total peripheral resistance and therefore systemic blood pressure. However, renal vasoconstriction in response to NOS inhibition is largely mediated by the unbridled influence of endogenous Ang II, especially when Ang II is increased.24

In summary, it has become clear that the balance between NO and Ang II, rather than the absolute concentration of either, is what determines their effect on cardiovascular and renal physiology and pathophysiology (Figure 1). The reasons for the imbalances between the substances are often unclear. An understanding of the relations between hypertension, end-organ damage, and the NO-Ang II axis leads one to believe that available therapeutic strategies capable of restoring the homeostatic balance of these vasoactive agents within the vessel wall would be effective in preventing or arresting end-organ disease.


*    Acknowledgments
 
This work was supported by research funds from the Veterans Affairs Administration. The author would like to thank Martha Heiberg and Barb Devereaux for secretarial assistance.

Received October 24, 2000; first decision November 30, 2000; accepted December 18, 2000.


*    References
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 *References
 

  1. Brunner HR, Gavras H. Early experience with angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors. In: Epstein M, Brunner HR, eds. Angiotensin II Receptor Antagonists. 1st ed. Philadelphia, Penn: Hanley & Belfus Inc; 2001:79–88.
  2. Wolf G, Ziyadeh FN. The role of angiotensin II in diabetic nephropathy: emphasis on nonhemodynamic mechanisms. Am J Kidney Dis. 1997;29:153–163.[Medline] [Order article via Infotrieve]
  3. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–376.[Medline] [Order article via Infotrieve]
  4. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987;84:9265–9269.
  5. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991;43:109–142.[Medline] [Order article via Infotrieve]
  6. Raij L, Baylis C. Glomerular actions of nitric oxide. Kidney Int. 1995;48:20–32.[Medline] [Order article via Infotrieve]
  7. Campbell DJ, Habener JF. Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat. J Clin Invest. 1986;78:31–39.
  8. Ganten D, Hermann K, Unger T, Lang RE. The tissue renin-angiotensin systems: focus on brain angiotensin, adrenal gland and arterial wall. Clin Exp Hypertens. 1983;5:1099–1118.
  9. Navar LG, Imig JD, Zou L, Wang CT. Intrarenal production of angiotensin II. Semin Nephrol. 1997;17:412–422.[Medline] [Order article via Infotrieve]
  10. Takemoto M, Egashira K, Usui M, Numaguchi K, Tomita H, Tsutsui H, Shimokawa H, Sueishi K, Takeshita A. Important role of tissue angiotensin-converting enzyme activity in the pathogenesis of coronary vascular and myocardial structural changes induced by long-term blockade of nitric oxide synthesis in rats. J Clin Invest. 1997;99:278–287.[Medline] [Order article via Infotrieve]
  11. Ichiki T, Usui M, Kato M, Funakoshi Y, Ito K, Egashira K, Takeshita A. Downregulation of angiotensin II type 1 receptor gene transcription by nitric oxide. Hypertension. 1998;31:342–348.[Abstract/Free Full Text]
  12. Usui M, Ichiki T, Katoh M, Egashira K, Takeshita A. Regulation of angiotensin II receptor expression by nitric oxide in rat adrenal gland. Hypertension. 1998;32:527–533.[Abstract/Free Full Text]
  13. Awolesi MA, Widmann MD, Sessa WC, Sumpio BE. Cyclic strain increases endothelial nitric oxide synthase activity. Surgery. 1994;116:439–444.[Medline] [Order article via Infotrieve]
  14. Hambrecht R, Wolf A, Gielen S, Linke A, Hofer J, Erbs S, Schoene M, Schuler G. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med. 2000;342:454–460.[Abstract/Free Full Text]
  15. Harrison DG, Galis Z, Parthasarathy S, Griendling KK. Oxidative stress and hypertension. In: Izzo JL, Black HR, eds. Hypertension Primer. 2 ed. Dallas, Texas: Lippincott Williams & Wilkins; 1999:163–166.
  16. Ganier JV, Morrow JD, Loveland A, King DJ, Brown NJ. Effect of bradykinin-receptor blockade on the response to angiotensin converting–enzyme inhibitor in normotensive and hypertensive subjects. N Engl J Med. 1998;339:1285–1292.[Abstract/Free Full Text]
  17. Goodfriend TL, Elliott ME, Catt KJ. Angiotensin receptors and their antagonists. N Engl J Med. 1996;334:1649–1654.[Free Full Text]
  18. Liu YH, Yang XP, Sharov VG, Nass O, Sabbah HN, Peterson E, Carretero OA. Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure: role of kinins and angiotensin II type 2 receptors. J Clin Invest. 1999;99:1826–1935.
  19. Griendling KK, Lassegue B, Alexander RW. Angiotensin receptors and their therapeutic implications. Annu Rev Pharmacol Toxicol. 1996;36:281–306.[Medline] [Order article via Infotrieve]
  20. Timmermans PB, Wong PC, Chiu AT, Herblin WF, Benfield P, Carini DJ, Lee RJ, Wexler RR, Saye JA, Smith RD. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev. 1993;45:205–251.[Medline] [Order article via Infotrieve]
  21. Hutchinson HG, Hein L, Fujinaga M, Pratt RE. Modulation of vascular development and injury by angiotensin II. Cardiovasc Res. 1999;41:689–700.[Abstract/Free Full Text]
  22. Carey RM, Wang ZQ, Siragy HM. Role of the angiotensin type 2 receptor in the regulation of blood pressure and renal function. Hypertension. 2000;35(pt 2):155–163.
  23. Stoll M, Steckelings UM, Paul M, Bottari SP, Metzger R, Unger T. The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest. 1995;95:651–657.
  24. Beierwaltes WH, Sigmon DH. Angiotensin-nitric oxide interaction and the regulation of renal vascular tone. In: Sowers JR, ed. Endocrinology of the Vasculature. 1st ed. Totowa, NJ: Human Press Inc; 1996:109–123.
  25. Navar LG, Harrison-Bernard LM, Imig JD, Mitchell KD. Renal actions of angiotensin II and AT1 receptor blockers. In: Epstein M, Brunner HR, eds. Angiotensin II Receptor Antagonists. 1st ed. Philadelphia, Penn: Hanley & Belfus Inc; 2001:189–214.
  26. Raij L, Hayakawa H, Jaimes EA. Cardio-renal injury and nitric oxide synthase activity in hypertension. J Hypertens. 1998;16(suppl 8):S69–S73.
  27. Denton KM, Fennessy PA, Alcorn D, Anderson WP. Morphometric analysis of the actions of angiotensin II on renal arterioles and glomeruli. Am J Physiol. 1992;262:F367–F372.[Abstract/Free Full Text]
  28. Alberola AM, Salazar FJ, Nakamura T, Granger JP. Interaction between angiotensin II and nitric oxide in control of renal hemodynamics in conscious dogs. Am J Physiol. 1994;267:R1472–R1478.[Abstract/Free Full Text]
  29. Ito S, Arima S, Ren YL, Juncos LA, Carretero OA. Endothelium-derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole. J Clin Invest. 1993;91:2012–2019.
  30. Arima S, Endo Y, Yaoita H, Omata K, Ogawa S, Tsunoda K, Abe M, Takeuchi K, Abe K, Ito S. Possible role of P-450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II type 2 receptor in the isolated microperfused rabbit afferent arteriole. J Clin Invest. 1997;100:2816–2823.[Medline] [Order article via Infotrieve]
  31. Deng A, Baylis C. Locally produced EDRF controls preglomerular resistance and ultrafiltration coefficient. Am J Physiol. 1993;264:F212–F215.[Abstract/Free Full Text]
  32. Ohishi K, Carmines PK, Inscho EW, Navar LG. EDRF-angiotensin II interactions in rat juxtamedullary afferent and efferent arterioles. Am J Physiol. 1992;263:F900–F906.[Abstract/Free Full Text]
  33. Madrid MI, Garcia-Salom M, Tornel J, de Gasparo M, Fenoy FJ. Interactions between nitric oxide and angiotensin II on renal cortical and papillary blood flow. Hypertension. 1997;30:1175–1182.[Abstract/Free Full Text]
  34. Brands MW, Hall JE. Mechanism for chronic antihypertensive effect of angiotensin II blockade. In: Epstein M, Brunner HR, eds. Angiotensin II Receptor Antagonists. 1st ed. Philadelphia, Penn: Hanley & Belfus Inc; 2001:171–188.
  35. Gabbai FB, Blantz RC. Role of nitric oxide in renal hemodynamics. Semin Nephrol. 1999;19:242–250.[Medline] [Order article via Infotrieve]
  36. Mattson DL, Lu S, Nakanishi K, Papanek PE, Cowley AW, Jr. Effect of chronic renal medullary nitric oxide inhibition on blood pressure. Am J Physiol. 1994;266:H1918–H1926.[Abstract/Free Full Text]
  37. Panza JA, Quyyumi AA, Brush JE, Jr, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323:22–27.[Abstract]
  38. Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA. Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation. 1993;87:1468–1474.[Abstract/Free Full Text]
  39. Cardillo C, Kilcoyne CM, Cannon RO 3rd, Panza JA. Racial differences in nitric oxide-mediated vasodilator response to mental stress in the forearm circulation. Hypertension. 1998;31:1235–1239.[Abstract/Free Full Text]
  40. Taddei S, Virdis A, Mattei P, Ghiadoni L, Sudano I, Salvetti A. Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation. 1996;94:1298–1303.[Abstract/Free Full Text]
  41. Gaeta G, De Michele M, Cuomo S, Guarini P, Foglia MC, Bond G, Trevisan M. Arterial abnormalities in the offspring of patients with premature myocardial infarction. N Engl J Med. 2000;343:840–846.[Abstract/Free Full Text]
  42. Huang PL, Huang Z, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA, Fishman MC. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature. 1995;377:239–242.[Medline] [Order article via Infotrieve]
  43. Ohashi Y, Kawashima S, Hirata K, Yamashita T, Ishida T, Inoue N, Sakoda T, Kurihara H, Yazaki Y, Yokoyama M. Hypotension and reduced nitric oxide-elicited vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase. J Clin Invest. 1998;102:2061–2071.[Medline] [Order article via Infotrieve]
  44. Linder L, Kiowski W, Buhler FR, Luscher TF. Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo: blunted response in essential hypertension. Circulation. 1990;81:1762–1767.[Abstract/Free Full Text]
  45. Raij L. Nitric oxide in hypertension: relationship with renal injury and left ventricular hypertrophy [published erratum appears in Hypertension 1998 Jun;31:1357]. Hypertension. 1998;31:189–193.[Abstract/Free Full Text]
  46. Schiffrin EL. State-of-the-art lecture: role of endothelin-1 in hypertension. Hypertension. 1999;34(pt 2):876–881.
  47. Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med. 1994;330:1431–1438.[Free Full Text]
  48. Rudic RD, Shesely EG, Maeda N, Smithies O, Segal SS, Sessa WC. Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling. J Clin Invest. 1998;101:731–736.[Medline] [Order article via Infotrieve]
  49. Cayette AJ, Palcino JJ, Hortens K, Cohen R. Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscler Thromb. 1994;14:753–759.[Abstract/Free Full Text]
  50. Craven PA, Studer RK, Felder J, Phillips S, DeRubertis FR. Nitric oxide inhibition of transforming growth factor-ß and collagen synthesis in mesangial cells. Diabetes. 1997;46:671–681.[Abstract]
  51. Ketteler M, Noble NA, Border WA. Transforming growth factor-ß and angiotensin II: the missing link from glomerular hyperfiltration to glomerulosclerosis? Annu Rev Physiol. 1995;57:279–295.[Medline] [Order article via Infotrieve]
  52. Kannel WB. Blood pressure as a cardiovascular risk factor: prevention and treatment. JAMA. 1996;275:1571–1576.[Abstract]
  53. Bakris GL, Re RN. Endothelin modulates angiotensin II-induced mitogenesis of human mesangial cells. Am J Physiol. 1993;264:F937–F942.[Abstract/Free Full Text]
  54. Steudel W, Scherrer-Crosbie M, Bloch KD, Weimann J, Huang PL, Jones RC, Picard MH, Zapol WM. Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital deficiency of nitric oxide synthase 3. J Clin Invest. 1998;101:2468–2477.[Medline] [Order article via Infotrieve]
  55. Von der Leyen HE, Gibbons GH, Morishita R, Lewis NP, Zhang L, Nakajima M, Kaneda Y, Cooke JP, Dzau VJ. Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene. Proc Natl Acad Sci U S A. 1995;92:1137–1141.[Abstract/Free Full Text]
  56. Boulanger C, Luscher TF. Release of endothelin from the porcine aorta: inhibition by endothelium-derived nitric oxide. J Clin Invest. 1990;85:587–590.
  57. Kashiwagi M, Shinozaki M, Hirakata H, Tamaki K, Hirano T, Tokumoto M, Goto H, Okuda S, Fujishima M. Locally activated renin-angiotensin system associated with TGF-ß1 as a major factor for renal injury induced by chronic inhibition of nitric oxide synthase in rats. J Am Soc Nephrol. 2000;11:616–624.[Abstract/Free Full Text]
  58. Prasad A, Tupas-Habib T, Schenke WH, Mincemoyer R, Panza JA, Waclawin MA, Ellahham S, Quyyumi AA. Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis. Circulation. 2000;101:2349–2354.[Abstract/Free Full Text]
  59. Jaimes EA, Galceran JM, Raij L. Angiotensin II induces superoxide anion production by mesangial cells. Kidney Int. 1998;54:775–784.[Medline] [Order article via Infotrieve]
  60. Pagano PJ, Chanock SJ, Siwik DA, Colucci WS, Clark JK. Angiotensin II induces p67phox mRNA expression and NADPH oxidase superoxide generation in rabbit aortic adventitial fibroblasts. Hypertension. 1998;32:331–337.[Abstract/Free Full Text]
  61. Bataineh A, Raij L. Angiotensin II, nitric oxide, and end-organ damage in hypertension. Kidney Int Suppl. 1998;68:S14–S19.[Medline] [Order article via Infotrieve]
  62. Hayakawa H, Raij L. The link among nitric oxide synthase activity, endothelial function, and aortic and ventricular hypertrophy in hypertension. Hypertension. 1997;29:235–241.[Abstract/Free Full Text]
  63. Hayakawa H, Raij L. Nitric oxide synthase activity and renal injury in genetic hypertension. Hypertension. 1998;31:266–270.[Abstract/Free Full Text]
  64. Bigazzi R, Bianchi S, Baldari D, Sgherri G, Baldari G, Campese VM. Microalbuminuria in salt-sensitive patients: a marker for renal and cardiovascular risk factors. Hypertension. 1994;23:195–199.[Abstract/Free Full Text]
  65. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent: a novel action of insulin to increase nitric oxide release. J Clin Invest. 1994;94:1172–1179.
  66. Baron AD, Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G. Insulin-mediated skeletal muscle vasodilation contributes to both insulin sensitivity and responsiveness in lean humans. J Clin Invest. 1995;96:786–792.
  67. Reaven GM, Twersky J, Chang H. Abnormalities of carbohydrate and lipid metabolism in Dahl rats. Hypertension. 1991;18:630–635.[Abstract/Free Full Text]
  68. Miyoshi A, Suzuki H, Fujiwara M, Masai M, Iwasaki T. Impairment of endothelial function in salt-sensitive hypertension in humans. Am J Hypertens. 1997;10:1083–1090.[Medline] [Order article via Infotrieve]
  69. Weinberger MH, Fineberg NS. Sodium and volume sensitivity of blood pressure: age and pressure change over time. Hypertension. 1991;18:67–71.[Abstract/Free Full Text]
  70. Schuster H, Wienker TF, Toka HR, Bahring S, Jeschke E, Toka O, Busjahn A, Hempel A, Tahlhammer C, Oelkers W, Kunze J, Bilginturan N, Haller H, Luft FC. Autosomal dominant hypertension and brachydactyly in a Turkish kindred resembles essential hypertension. Hypertension. 1996;28:1085–1092.[Abstract/Free Full Text]
  71. Campese VM. Salt sensitivity in hypertension: renal and cardiovascular implications. Hypertension. 1994;23:531–550.[Abstract/Free Full Text]
  72. Raij L. Nitric oxide, salt sensitivity, and cardiorenal injury in hypertension. Semin Nephrol. 1999;19:296–303.[Medline] [Order article via Infotrieve]
  73. Mogensen CE, Christensen CK, Christensen NJ, Gundersen HJ, Jacobsen FK, Pedersen EB, Vittinghus E. Renal protein handling in normal, hypertensive and diabetic man. Contrib Nephrol. 1981;24:139–152.[Medline] [Order article via Infotrieve]
  74. Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, Sanchez-Pascuala R, Hernandez G, Diaz C, Lamas S. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest. 1998;101:2711–2719.[Medline] [Order article via Infotrieve]
  75. Heimann JC, Drumond S, Alves AT, Barbato AJ, Dichtchekenian V, Marcondes M. Left ventricular hypertrophy is more marked in salt-sensitive than in salt-resistant hypertensive patients. J Cardiovasc Pharmacol. 1991;17:S122–S124.
  76. Morimoto A, Uzu T, Fujii T, Nishimura M, Kuroda S, Nakamura S, Inenaga T, Kimura G. Sodium sensitivity and cardiovascular events in patients with essential hypertension. Lancet. 1997;350:1734–1737.[Medline] [Order article via Infotrieve]
  77. London GM, Levenson JA, London AM, Simon AC, Safar ME. Systemic compliance, renal hemodynamics, and sodium excretion in hypertension. Kidney Int. 1984;26:342–350.[Medline] [Order article via Infotrieve]
  78. Cardillo C, Kilcoyne CM, Quyyumi AA, Cannon RO 3rd, Panza JA. Selective defect in nitric oxide synthesis may explain the impaired endothelium-dependent vasodilation in patients with essential hypertension. Circulation. 1998;97:851–856.[Abstract/Free Full Text]
  79. Luscher TF, Raij L, Vanhoutte PM. Endothelium-dependent vascular responses in normotensive and hypertensive Dahl rats. Hypertension. 1987;9:157–163.[Abstract/Free Full Text]
  80. Overlack A, Ruppert M, Kolloch R, Kraft K, Stumpe KO. Age is a major determinant of the divergent blood pressure responses to varying salt intake in essential hypertension. Am J Hypertens. 1995;8:829–836.[Medline] [Order article via Infotrieve]
  81. Taddei S, Virdis A, Mattei P, Ghiadoni L, Gennari A, Fasolo CB, Sudano I, Salvetti A. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation. 1995;91:1981–1987.[Abstract/Free Full Text]
  82. Tolins JP, Palmer RM, Moncada S, Raij L. Role of endothelium-derived relaxing factor in regulation of renal hemodynamic responses. Am J Physiol. 1990;258:H655–H662.[Abstract/Free Full Text]
  83. Tolins JP, Raij L. Effects of amino acid infusion on renal hemodynamics: role of endothelium-derived relaxing factor. Hypertension. 1991;17:1045–1051.[Abstract/Free Full Text]
  84. Baylis C, Engels K, Samsell L, Harton P. Renal effects of acute endothelial-derived relaxing factor blockade are not mediated by angiotensin II. Am J Physiol. 1993;264:F74–F78.[Abstract/Free Full Text]
  85. Pucci ML, Lin L, Nasjletti A. Pressor and renal vasoconstrictor effects of NG-nitro-L-arginine as affected by blockade of pressor mechanisms mediated by the sympathetic nervous system, angiotensin, prostanoids and vasopressin. J Pharmacol Exp Ther. 1992;261:240–245.[Abstract/Free Full Text]
  86. Baylis C, Harvey J, Engels K. Acute nitric oxide blockade amplifies the renal vasoconstrictor actions of angiotensin II. J Am Soc Nephrol. 1994;5:211–214.[Abstract]
  87. Wilcox CS, Welch WJ, Murad F, Gross SS, Taylor G, Levi R, Schmidt HH. Nitric oxide synthase in macula densa regulates glomerular capillary pressure. Proc Natl Acad Sci U S A. 1992;89:11993–11997.[Abstract/Free Full Text]
  88. Sigmon DH, Carretero OA, Beierwaltes WH. Angiotensin dependence of endothelium-mediated renal hemodynamics. Hypertension. 1992;20:643–650.[Abstract/Free Full Text]
  89. Mattson DL, Roman RJ, Cowley AW Jr. Role of nitric oxide in renal papillary blood flow and sodium excretion. Hypertension. 1992;19:766–769.[Abstract/Free Full Text]
  90. Salazar FJ, Pinilla JM, Lopez F, Romero JC, Quesada T. Renal effects of prolonged synthesis inhibition of endothelium-derived nitric oxide. Hypertension. 1992;20:113–117.[Abstract/Free Full Text]
  91. Ribeiro MO, Antunes E, de Nucci G, Lovisolo SM, Zatz R. Chronic inhibition of nitric oxide synthesis: a new model of arterial hypertension. Hypertension. 1992;20:298–303.[Abstract/Free Full Text]
  92. Pollock DM, Polakowski JS, Divish BJ, Opgenorth TJ. Angiotensin blockade reverses hypertension during long-term nitric oxide synthase inhibition. Hypertension. 1993;21:660–666.[Abstract/Free Full Text]
  93. Morton JJ, Beattie EC, Speirs A, Gulliver F. Persistent hypertension following inhibition of nitric oxide formation in the young Wistar rat: role of renin and vascular hypertrophy. J Hypertens. 1993;11:1083–1088.[Medline] [Order article via Infotrieve]



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