This Article Abstract Full Text (PDF) All Versions of this Article: 41/6/1359    most recent 01.HYP.0000070958.39174.7Ev1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vassileva, I. Articles by Pollock, D. M. Search for Related Content PubMed PubMed Citation Articles by Vassileva, I. Articles by Pollock, D. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB SODIUM CHLORIDE Related Collections Cardio-renal physiology/pathophysiology Hypertension - basic studies Endothelium/vascular type/nitric oxide

(Hypertension. 2003;41:1359.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Functional Role of ET_B Receptors in the Renal Medulla

From the Vascular Biology Center, Departments of Surgery, Physiology, and Pharmacology and Toxicology, Medical College of Georgia, Augusta.

Correspondence to David M. Pollock, PhD, Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd, Augusta, GA 30912-2500. E-mail dpollock{at}mail.mcg.edu

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Experiments were conducted to determine the influence of ET_B receptors in the control of renal medullary function. The acute relation between renal perfusion pressure (RPP) and natriuresis was examined in anesthetized rats treated with the ET_B antagonist A-192621 (10 mg/kg IV). In A-192621–treated rats, sodium excretion (UNaV) was 0.4±0.1, 0.6±0.3, and 2.7±0.5 µmol/min at RPP of 80±1, 107±1, and 144±5 mm Hg, respectively. In control rats, UNaV averaged 0.8±0.4, 3.4±1.2, and 8.1±1.7 µmol/min at RPP of 77±2, 115±5, and 137±3 mm Hg, respectively. For normal and high RPP, UNaV was significantly lower in A-192621–treated rats compared with control rats. Additional experiments determined the effects of Big ET-1 (10 pmol/kg per minute) on intrarenal blood flow. Medullary blood flow (MBF) and cortical blood flow were measured in anesthetized rats by single-fiber, laser Doppler flowmetry. Cortical blood flow significantly decreased in response to Big ET-1 in rats on a normal or high salt diet. Big ET-1 significantly increased MBF in rats on a high salt diet, whereas there was no change in MBF in rats on a normal salt diet. These results demonstrate that medullary vasodilation produced by Big ET-1 is more prominent in rats on a high salt diet and are consistent with a contribution of ET_B-mediated events in the natriuretic response to high salt intake. Taken together, these findings support the hypothesis that endothelin plays an important role in regulating sodium excretion through activation of ET_B receptors.

Key Words: endothelin • receptors, endothelin • natriuresis • blood flow

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Cowley, Roman, and colleagues¹ have provided much of the evidence demonstrating that changes in blood flow and renal tubular reabsorption within the renal medulla contribute significantly to the relation between blood pressure and changes in sodium and water excretion. The renal medulla is a major site of endothelin production and is the location with the highest concentration of endothelin B (ET_B) receptors.² The ET_B receptor has several distinct functions on both intrarenal hemodynamics and tubular reabsorption within the renal medulla that may play a role in arterial pressure regulation. Hoffman and colleagues³ recently observed that the diuretic and natriuretic responses to the ET-1 precursor Big ET-1 can be inhibited by an ET_B receptor antagonist. These investigators have also reported that Big ET-1 vasodilates the renal medullary circulation despite cortical and systemic vasoconstriction.⁴ In addition, several studies have provided evidence that renal tubular ET_B receptors serve to inhibit reabsorption of sodium in the thick ascending limb and collecting duct.^5,6

Our laboratory recently completed a study examining the effects of salt intake on the response to chronic ET_B receptor blockade.⁷ The chronic hypertension produced by ET_B receptor blockade was exaggerated in animals on a high salt diet. The high concentration of ET_B receptors in the medulla and their described effects on the medullary circulation and on sodium and water reabsorption led us to hypothesize that the ET_B receptors may play a role in the pressure natriuresis and diuresis phenomenon. Studies from our laboratory have also shown that ET_B receptors are upregulated in the kidneys of DOCA-salt hypertensive rats⁸ and that urinary ET-1 excretion is significantly increased in rats on a high salt diet.⁷ Taken together, these observations have led us to propose that ET_B-mediated vasodilation may be an important component of the functional response to increased dietary salt intake.

Experiments in the present study were conducted test the hypothesis that ET_B receptor function is necessary to maintain the normal pressure-natriuresis relation. Acute pressure natriuresis curves were generated before and after receptor ET_B blockade in anesthetized rats. Experiments were also conducted to determine the ability of Big ET-1 to produce medullary vasodilation during conditions of high salt intake.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Pressure-Natriuresis Studies
The effect of ET_B receptor blockade on the relation between acute changes in renal perfusion pressure and urinary sodium and water excretion was determined in male Sprague-Dawley rats (220 to 250 g, Harlan Laboratories). Rats were anesthetized with Inactin (50 mg/kg IP) and surgically prepared for renal clearance measurements as previously described.⁹ Ligatures were placed around the upper mesentery and the celiac arteries and the aorta just proximal and distal to the renal arteries to control renal perfusion pressure. Glomerular filtration rate (GFR) was measured by intravenous infusion of saline containing [³H]inulin (4 µCi/h per 100 g; Amersham Pharmacia Biotech).

After surgical preparation, rats were given an intravenous bolus injection of either vehicle (saline) or the ET_B antagonist A-192621 (10 mg/kg). A-192621 is selective for the ET_B receptor (IC₅₀=8.2 µmol/L for ET_A and 6.4 nmol/L for ET_B), with a half-life of >6 hours.¹⁰ Fifteen minutes later, renal perfusion pressure was set sequentially at low (80 mm Hg), normal (110 mm Hg), and high (>130 mm Hg) levels and was maintained at each level for 30 minutes. Urine was collected during the final 20 minutes of each period.

Renal Blood Flow Autoregulation Studies
Animals were prepared as described above except that renal blood flow (RBF) was measured with an ultrasonic probe placed on the renal artery. Renal perfusion pressure was controlled by an adjustable constricting ligature placed on the abdominal aorta. Renal perfusion pressure was reduced in increments of 10 mm Hg for 1 to 2 minutes starting at spontaneous arterial pressure down to 70 mm Hg. After generating 2 to 3 control autoregulatory curves, rats were given A-192621 and 15 minutes later, a series of 2 to 3 autoregulatory curves were again generated.

Intrarenal Blood Flow Studies
A final series of experiments were conducted to determine whether a high salt diet would influence the renal hemodynamic response to Big ET-1 infusion. Sprague-Dawley rats were maintained on either normal sodium (0.8% NaCl) or high sodium (10% NaCl) diet for 1 week. Rats were then anesthetized and surgically prepared as described above. Medullary blood flow and cortical blood flow (MBF and CBF, respectively) were measured by single-fiber, laser Doppler flowmetry, based on the technique of Mattson et al.¹¹ After a 30-minute period of recovery from surgery, a 30-minute control period was obtained. Rats were then given an intravenous bolus of either saline or A-192621. Fifteen minutes after the antagonist was given, Big ET-1 was infused for 1 hour at a dose 10 pmol/kg per minute (20 µL/min). Control groups received vehicle (0.9% NaCl). The function of the laser Doppler fibers was verified at the beginning of the experiment by recording the changes of the regional blood flow in response to compression of the aorta above the renal arteries. Positioning of the fibers was verified at the end of the experiments by dissection.

Analytical and Statistical Analysis
Urine sodium concentrations were measured with the use of ion-selective electrodes (EL-ISE; Beckman Instruments). ANOVA or ANOVA for repeated measures was used along with means comparison contrasts to determine differences between individual means among groups (SuperANOVA, Abacus Concepts).

	Results

Top Abstract Introduction Methods Results Discussion References

 
Pressure-Natriuresis Studies
Adjusting renal perfusion pressure to 77±2, 115±5, and 137±3 mm Hg in untreated, control rats increased urine flow from 11.3±2.8 to 23.2±5.2 to 52.8±8.7 µL/min, respectively (Figure 1). In rats treated with the ET_B antagonist, A-192621, the pressure-diuresis relation was blunted, with renal perfusion pressures of 80±1, 107±1, and 144±5 mm Hg associated with urine flow rates of 9.4±1.3, 12.7±2.2, and 28.7±4.6 µL/min, respectively. For a given target range of arterial pressure, urine flow rate after antagonist treatment was significantly lower only at the highest renal perfusion pressure.

View larger version (17K): [in this window] [in a new window]   Figure 1. Urine flow rate, sodium excretion, and GFR at low, normal, and high renal perfusion pressures in rats pretreated with ETB antagonist A-192621 (10 mg/kg IV) or vehicle (1 mL/kg). *P<0.05 vs vehicle-treated rats. Vehicle-treated group, n=9; group pretreated with ETB antagonist A-192621, n=11. Number of the rats in which GFR data were obtained was 5 and 6 for vehicle and A-192621 groups, respectively.

Sodium excretion in control rats averaged 0.8±0.4, 3.4±1.2, and 8.1±1.7 µmol/min at the low, normal, and high renal perfusion pressures, respectively (Figure 1). In A-192621–treated rats, the pressure-natriuresis curve was shifted to the right and the slope of the curve was decreased when compared with the curve for the vehicle-treated rats. Sodium excretion was 0.4±0.1, 0.6±0.3, and 2.7±0.5 µmol/min at the low, normal, and high renal perfusion pressures, respectively, in A-192621–treated rats. For the 2 higher levels of renal perfusion pressure, sodium excretion was significantly lower in rats treated with A-192621 compared with control rats.

For the high renal perfusion pressure, GFR was not significantly different between control and A-192621-treated rats (Figure 1). However, at the low and normal target range of pressures, GFR was significantly lower in A-192621–treated rats compared with control rats: 1.0±0.23 versus 2.0±0.13 mL/min at the low pressure and 1.6±0.26 versus 2.7±0.42 mL/min at the normal pressure range.

RBF Autoregulation
Whole-kidney RBF autoregulatory responses were determined before and after treatment with the ET_B antagonist A-192621 (Figure 2). Spontaneous arterial pressure averaged 106.8±3 mm Hg during the baseline period and was significantly increased after administration of A-192621 (120.6±4 mm Hg, P<0.05). As renal perfusion pressure was decreased sequentially from the spontaneous pressure to 70 mm Hg in 10 mm Hg decrements, RBF was maintained fairly steady during the control period. After treatment with the ET_B antagonist, baseline RBF was significantly reduced; however, RBF autoregulatory capability appeared to be maintained efficiently.

View larger version (24K): [in this window] [in a new window]   Figure 2. RBF autoregulation curves in rats during control period and after treatment with the ETB antagonist A-192621 (10 mg/kg IV) (n=7).

Intrarenal Blood Flow Studies
Intravenous infusion of Big ET-1 significantly increased mean arterial pressure to a similar extent in rats on a high salt diet compared with those on a normal salt diet (Figure 3A). Administration of the ET_B receptor antagonist A-192621 produced a significant increase in the magnitude of the response to Big ET-1. This increase was not influenced by increased salt intake (Figure 3B). Within the kidney, Big ET-1 decreased CBF to a similar extent in rats on normal and high salt diets (Figure 4A). Prior administration of A-192621 exaggerated the effects of Big ET-1 on CBF. These changes again were not influenced by dietary salt. In contrast, changes in MBF were highly dependent on dietary salt levels (Figure 4B). Big ET-1 had no effect on MBF in rats on a normal salt diet with or without ET_B receptor blockade. However, in rats on a high salt diet, Big ET-1 produced a significant increase in MBF that was completely blocked by ET_B receptor blockade. In fact, MBF significantly decreased after Big ET-1 infusion in rats on a high salt diet given the ET_B receptor antagonist. In separate groups of time control experiments, an identical protocol was used but without Big ET-1 infusion (Figure 5). A-192621 produced a significant decrease in both CBF and MBF in rats on a normal salt diet. These results are consistent with changes in total RBF, as observed in autoregulation experiments. No changes in either CBF or MBF were observed in rats given only saline over the time course of these experiments.

View larger version (28K): [in this window] [in a new window]   Figure 3. A, Mean arterial pressure in rats on a normal or high salt diet. Rats were given ETB receptor antagonist A-192621 (10 mg/kg IV) followed by constant infusion of Big ET-1 (10 pmol/kg per minute). B, Change in mean arterial pressure compared with baseline during final 30 minutes of Big ET-1 infusion. n=5 to 8 in each group. *P<0.05 vs vehicle-treated rats.

View larger version (24K): [in this window] [in a new window]   Figure 4. Changes in CBF (A) and MBF (B) in response to A-192621 (10 mg/kg IV) and Big ET-1 (10 pmol/kg per minute IV). n=5 to 8 in each group. *P<0.05 vs baseline before Big ET-1; P<0.05 vs rats treated with A-192621 on similar salt diet.

View larger version (17K): [in this window] [in a new window]   Figure 5. Changes in CBF (A) and MBF (B) in response to A-192621 (10 mg/kg IV) or saline (0.9% NaCl). n=5 in each group. *P<0.05 vs initial flow; P<0.05 vs rats treated with A-192621 on similar salt diet.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
Results from the current study provide several lines of evidence to support the hypothesis that ET_B receptors play an important role in the control of renal medullary function. We observed that the acute loss of ET_B receptor function severely blunts the normal relation between renal perfusion pressure and sodium and water excretion. In addition, we observed that Big ET-1 at 10 pmol/kg per minute significantly increased MBF in rats on a high salt diet but not in rats on a normal salt diet. This finding is consistent with the idea that the functional response to a high salt diet includes increased capacity for ET_B-induced medullary vasodilation.

The current study extends the previous work from our laboratory demonstrating that long-term ET_B receptor blockade results in hypertension that is exacerbated by high salt intake.⁷ Furthermore, we have observed that ET_B receptors within the kidney are upregulated in a model of high salt hypertension, the DOCA-salt–treated rat.⁸ This model is characterized by elevated endothelin synthesis and ET_A-dependent hypertension.^12–14 Together, these studies provide evidence that endothelin may participate in the long-term adaptation of the pressure-natriuresis relation and suggest that endothelin plays a role in regulating arterial pressure during conditions of high salt intake. Further support for this hypothesis is demonstrated by the observation that renal ET-1 production, as assessed by urinary ET-1 excretion, was increased during high salt intake.⁷ The current study extends these previous studies to suggest the mechanism for endothelin control of pressure natriuresis is through ET_B-dependent vasodilation.

The ET_B receptor is known to function in a variety of ways. Many of the effects of ET_B receptor blockade can be explained by increased ET-1 survival and subsequent ET_A receptor activation because of the reported clearance function of the ET_B receptor.¹⁵ However, there is considerable evidence that ET_B receptors located on renal tubular epithelium inhibit sodium and water reabsorption,^5,6,16 whereas those located on vascular endothelium mediate vasodilation.^17,18 Both of these mechanisms appear to account for the natriuretic and diuretic actions attributed to ET-1 and the ET_B receptor.^4,19,20 Although we cannot exclude the possibility that the effects of ET_B blockade on pressure natriuresis can be explained by increased ET_A receptor function, the change in Big ET-1–mediated changes in MBF are consistent with a role for ET_B-mediated vasodilation in the response to changes in renal sodium excretion. It is also important to note that whereas ET_B receptor blockade increases circulating ET-1 levels, urinary ET-1 excretion, often used as an index of intrarenal ET-1 production, increases with high salt intake but does not change during ET_B receptor blockade.⁷ Furthermore, the kidney does not clear ET-1 from the circulation.¹⁵ These findings again argue that the vasodilatory and tubular actions of ET_B receptors are responsible for the changes in the renal pressure-natriuresis relation during ET_B receptor blockade.

It is important to note that all of the effects of Big ET-1 require conversion to ET-1 because the renal vasoconstrictor, diuretic, and natriuretic effects of Big ET-1 are blocked by the endothelin-converting enzyme phosphoramidon.²¹ In the present study, we used Big ET-1 because we have previously observed that Big ET-1 produces a larger natriuretic and diuretic effect compared with ET-1 at doses that produce similar increases in arterial pressure.²² This is probably related to limited conversion of Big ET-1 to ET-1 in the cortical circulation and the larger decreases in GFR produced by ET-1. We have also previously observed that ET_A receptor blockade will completely block the pressor response to Big ET-1, yet the diuretic actions are unaffected.²² These observations are consistent with the ET_B receptor mediating the diuretic actions of ET-1.

One of the main findings of our study is that ET_B receptor blockade shifts the pressure diuresis and natriuresis curves to the right, so that higher renal perfusion pressures are needed for the same amount of sodium to be excreted. To assess whether changes in GFR could account for the change in the pressure-natriuresis relation, we determined the effect of ET_B blockade on GFR when renal perfusion pressure was maintained at 3 different levels. For the low and normal renal perfusion pressures, we found that ET_B blockade significantly decreased GFR but only at the 2 lower pressures. This result may be due to vasoconstriction associated with ET_B blockade. That is, reduced ET_B-dependent vasodilation and reduced clearance of ET-1, resulting in increased ET_A-dependent vasoconstriction. Therefore, reduced GFR could account for some but not all of the effect of ET_B blockade on the acute pressure-natriuresis relation. Despite reducing baseline renal blood flow, the results also indicated that ET_B blockade did not impede the ability of the kidney to autoregulate RBF. These hemodynamic results coupled with reduced pressure natriuresis during ET_B receptor blockade are consistent with a role for ET_B receptors in modulating renal medullary function. As discussed, our results suggest that changes in the pressure–natriuresis and diuresis relation could be attributed to vasodilatory and/or tubular effects of ET_B receptors. Nonetheless, these results alone are not the definitive link between ET_B receptors and control of medullary function, since they could be explained simply on the basis of increased ET_A receptor activation through reduced ET-1 clearance.

Using a moderately low dose of Big ET-1, we observed significant decreases in renal CBF with little change in MBF. When rats were placed on a high salt diet, we were able to discern a vasodilatory effect that was blocked by the ET_B antagonist. These results indicate that the vasodilatory capability of Big ET-1 is enhanced by a high salt diet and provide more compelling evidence that ET_B function is related to salt intake. It has been previously established that Big ET-1 can produce ET_B-dependent medullary vasodilation and that the diuretic and natriuretic effects of Big ET-1 are also ET_B-dependent.^3,4 We can therefore hypothesize that medullary ET_B receptors function to enhance the excretion of salt and water under conditions of high salt intake through vasodilation within the renal medulla.

Perspectives
Our results support an important role for endothelin and the ET_B receptor in the regulation of arterial pressure through the participation in pressure natriuresis and diuresis events. We further conclude that control of MBF is an important mechanism for this regulatory action. Specifically, we propose that ET_B receptors facilitate pressure natriuresis through increases in MBF. These actions work in concert with direct effects of ET_B receptor activation on tubular reabsorption. Nonetheless, the complex nature of ET_B receptor-mediated actions on both tubular and vascular sites will require further investigation into the mechanism of how ET_B receptor activation controls salt handling within the kidney.

	Acknowledgments

 
Dr Vassileva was supported by a Young Investigator Fellowship from the National Kidney Foundation, Georgia Affiliate. Ms Mountain was supported by a Dean’s Student Research Fellowship from the Medical College of Georgia. This work was supported by a grant from the National Institutes of Health (HL64776) and a Scientist Development Grant from the American Heart Association (D.M.P.).

Received February 20, 2003; first decision March 10, 2003; accepted March 27, 2003.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Cowley AW Jr, Mattson DL, Lu S, Roman RJ. The renal medulla and hypertension. Hypertension. 1995; 25: 663–673.[Abstract/Free Full Text]

2. Kitamura K, Tanaka T, Kato J, Ogawa T, Eto T, Tanaka K. Immunoreactive endothelin in rat kidney inner medulla: marked decrease in spontaneously hypertensive rats. Biochem Biophys Res Commun. 1989; 162: 38–44.[CrossRef][Medline] [Order article via Infotrieve]

3. Hoffman A, Abassi Z, Brodsky S, Ramadan R, Winaver J. Mechanisms of big endothelin-1-induced diuresis and natriuresis: role of ET(B) receptors. Hypertension. 2000; 35: 732–739.[Abstract/Free Full Text]

4. Gurbanov K, Rubinstein I, Hoffman A, Abassi Z, Better OS, Winaver J. Differential regulation of renal regional blood flow by endothelin-1. Am J Physiol: Renal Physiol. 1996; 271: F1166–F1172.[Abstract/Free Full Text]

5. Gallego MS, Ling BN. Regulation of amiloride-sensitive Na⁺ channels by endothelin-1 in distal nephron cells. Am J Physiol Renal Physiol. 1996; 271: F451–F460.[Abstract/Free Full Text]

6. Plato CF, Pollock DM, Garvin JL. Endothelin inhibits thick ascending limb chloride flux via ET_B receptor-mediated NO release. Am J Physiol Renal Physiol. 2000; 279: F334–F344.[Abstract/Free Full Text]

7. Pollock DM, Pollock JS. Evidence for endothelin involvement in the response to high salt. Am J Physiol Renal Physiol. 2001; 281: F144–F150.[Abstract/Free Full Text]

8. Pollock DM, Allcock GH, Pollock JS. Upregulation of endothelin B receptors in kidneys of DOCA-salt hypertensive rats. Am J Physiol Renal Physiol. 2000; 278: F279–F286.[Abstract/Free Full Text]

9. Pollock DM. Contrasting pharmacological ET_B receptor blockade with genetic ET_B deficiency in renal responses to big ET-1. Physiol Genomics. 2001; 6: 39–43.[Abstract/Free Full Text]

10. von Geldern TW, Tasker AS, Sorensen BK, Winn M, Szczepankiewicz BG, Dixon DB, Chiou WJ, Wang L, Wessale JL, Adler A, Marsh KC, Nguyen B, Opgenorth TJ. Pyrrolidine-3-carboxylic acids as endothelin antagonists, 4: side chain conformational restriction leads to ET(B) selectivity. J Med Chem. 1999; 42: 3668–3678.[CrossRef][Medline] [Order article via Infotrieve]

11. Mattson DL, Lu S, 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]

12. Allcock GH, Venema RC, Pollock DM. ET_A receptor blockade attenuates the hypertension but not renal dysfunction in DOCA-salt rats. Am J Physiol Reg Integ Comp Physiol. 1998; 275: R245–R252.[Abstract/Free Full Text]

13. Lariviere R, Day R, Schiffrin EL. Increased expression of endothelin-1 gene in blood vessels of deoxycorticosterone acetate-salt hypertensive rats. Hypertension. 1993; 21: 916–920.[Abstract/Free Full Text]

14. Schiffrin EL, Sventek P, Li JS, Turgeon A, Reudelhuber T. Antihypertensive effect of an endothelin receptor antagonist in DOCA-salt spontaneously hypertensive rats. Br J Pharmacol. 1995; 115: 1377–1381.[Medline] [Order article via Infotrieve]

15. Fukuroda T, Fukikawa T, Ozaki S, Ishikawa K, Yano M, Nishikibe M. Clearance of circulating endothelin-1 by ET_B receptors in rats. Biochem Biophys Res Commun. 1994; 199: 1461–1465.[CrossRef][Medline] [Order article via Infotrieve]

16. Zeidel ML, Brady HR, Kone BC, Gullans SR, Brenner BM. Endothelin, a peptide inhibitor of Na⁺-K⁺-ATPase in intact renal tubular epithelial cells. Am J Physiol Cell Physiol. 1989; 257: C1101–C1107.[Abstract/Free Full Text]

17. De Nucci G, Thomas R, D’Orléans-Juste P, Antunes E, Walder C, Warner TD, Vane JR. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci U S A. 1988; 85: 9797–9800.[Abstract/Free Full Text]

18. Warner TD, Mitchell JA, De Nucci G, Vane JR. Endothelin-1 and endothelin-3 release EDRF from isolated perfused arterial vessels of the rat and rabbit. J Cardiovasc Pharmacol. 1989; 13 (suppl 5): S85–S88.[Medline] [Order article via Infotrieve]

19. Harris PJ, Zhuo J, Mendelsohn FA, Skinner SL. Haemodynamic and renal tubular effects of low doses of endothelin in anaesthetized rats. J Physiol (Lond). 1991; 433: 25–39.[Abstract/Free Full Text]

20. Schnermann J, Lorenz JN, Briggs JP, Keiser JA. Induction of water diuresis by endothelin in rats. Am J Physiol Renal Fluid Elect Physiol. 1992; 263: F516–F526.

21. Pollock DM, Opgenorth TJ. Evidence for metalloprotease involvement in the in vivo effects of big endothelin 1. Am J Physiol Reg Integ Comp Physiol. 1991; 261: R257–R263.[Abstract/Free Full Text]

22. Pollock DM, Opgenorth TJ. ET_A receptor-mediated responses to endothelin-1 and big endothelin-1 in the rat kidney. Br J Pharmacol. 1994; 111: 729–732.[Medline] [Order article via Infotrieve]

This article has been cited by other articles:

				C. Xie and D. H. Wang Ablation of Transient Receptor Potential Vanilloid 1 Abolishes Endothelin-Induced Increases in Afferent Renal Nerve Activity: Mechanisms and Functional Significance Hypertension, December 1, 2009; 54(6): 1298 - 1305. [Abstract] [Full Text] [PDF]

				L. R. Stow, M. L. Gumz, I. J. Lynch, M. M. Greenlee, A. Rudin, B. D. Cain, and C. S. Wingo Aldosterone Modulates Steroid Receptor Binding to the Endothelin-1 Gene (edn1) J. Biol. Chem., October 30, 2009; 284(44): 30087 - 30096. [Abstract] [Full Text] [PDF]

				H.-Q. Feng, N. D. Weymouth, and D. C. Rockey Endothelin antagonism in portal hypertensive mice: implications for endothelin receptor-specific signaling in liver disease Am J Physiol Gastrointest Liver Physiol, July 1, 2009; 297(1): G27 - G33. [Abstract] [Full Text] [PDF]

				J. C. Sullivan, B. Wang, E. I. Boesen, G. D'Angelo, J. S. Pollock, and D. M. Pollock Novel use of ultrasound to examine regional blood flow in the mouse kidney Am J Physiol Renal Physiol, July 1, 2009; 297(1): F228 - F235. [Abstract] [Full Text] [PDF]

				D. Nakano and D. M. Pollock Contribution of Endothelin A Receptors in Endothelin 1-Dependent Natriuresis in Female Rats Hypertension, February 1, 2009; 53(2): 324 - 330. [Abstract] [Full Text] [PDF]

				M. Herrera, N. J. Hong, P. A. Ortiz, and J. L. Garvin Endothelin-1 Inhibits Thick Ascending Limb Transport via Akt-stimulated Nitric Oxide Production J. Biol. Chem., January 16, 2009; 284(3): 1454 - 1460. [Abstract] [Full Text] [PDF]

				A. W. Cowley Jr Renal Medullary Oxidative Stress, Pressure-Natriuresis, and Hypertension Hypertension, November 1, 2008; 52(5): 777 - 786. [Full Text] [PDF]

				M. P. Schneider, Y. Ge, D. M. Pollock, J. S. Pollock, and D. E. Kohan Collecting Duct-Derived Endothelin Regulates Arterial Pressure and Na Excretion via Nitric Oxide Hypertension, June 1, 2008; 51(6): 1605 - 1610. [Abstract] [Full Text] [PDF]

				D. Nakano, J. S. Pollock, and D. M. Pollock Renal medullary ETB receptors produce diuresis and natriuresis via NOS1 Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1205 - F1211. [Abstract] [Full Text] [PDF]

				M. P. Schneider, E. W. Inscho, and D. M. Pollock Attenuated vasoconstrictor responses to endothelin in afferent arterioles during a high-salt diet Am J Physiol Renal Physiol, April 1, 2007; 292(4): F1208 - F1214. [Abstract] [Full Text] [PDF]

				M. Wendel, L. Knels, W. Kummer, and T. Koch Distribution of Endothelin Receptor Subtypes ETA and ETB in the Rat Kidney J. Histochem. Cytochem., November 1, 2006; 54(11): 1193 - 1203. [Abstract] [Full Text] [PDF]

				U. C. Kopp, M. Z. Cicha, and L. A. Smith Differential effects of endothelin on activation of renal mechanosensory nerves: stimulatory in high-sodium diet and inhibitory in low-sodium diet Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1545 - R1556. [Abstract] [Full Text] [PDF]

				M. Opocensky, H. J. Kramer, A. Backer, Z. Vernerova, V. Eis, L. Cervenka, V. Certikova Chabova, V. Tesar, and I. Vaneckova Late-Onset Endothelin-A Receptor Blockade Reduces Podocyte Injury in Homozygous Ren-2 Rats Despite Severe Hypertension Hypertension, November 1, 2006; 48(5): 965 - 971. [Abstract] [Full Text] [PDF]

				A. J. Bagnall, N. F. Kelland, F. Gulliver-Sloan, A. P. Davenport, G. A. Gray, M. Yanagisawa, D. J. Webb, and Y. V. Kotelevtsev Deletion of Endothelial Cell Endothelin B Receptors Does Not Affect Blood Pressure or Sensitivity to Salt Hypertension, August 1, 2006; 48(2): 286 - 293. [Abstract] [Full Text] [PDF]

				X. Guo and T. Yang Endothelin B receptor antagonism in the rat renal medulla reduces urine flow rate and sodium excretion. Experimental Biology and Medicine, June 1, 2006; 231(6): 1001 - 1005. [Abstract] [Full Text] [PDF]

				N. Dhaun, J. Goddard, and DavidJ. Webb The Endothelin System and Its Antagonism in Chronic Kidney Disease J. Am. Soc. Nephrol., April 1, 2006; 17(4): 943 - 955. [Abstract] [Full Text] [PDF]

				J. M. Williams, X. Zhao, M. H. Wang, J. D. Imig, and D. M. Pollock Peroxisome Proliferator-Activated Receptor-{alpha} Activation Reduces Salt-Dependent Hypertension During Chronic Endothelin B Receptor Blockade Hypertension, August 1, 2005; 46(2): 366 - 371. [Abstract] [Full Text] [PDF]

				J. L. Garvin and M. Herrera Physiological actions of renal collecting duct endothelin Am J Physiol Renal Physiol, May 1, 2005; 288(5): F910 - F911. [Full Text] [PDF]

				M. Ohkita, Y. Wang, N. D. T. Nguyen, Y.-H. Tsai, S. C. Williams, R. C. Wiseman, P. D. Killen, S. Li, M. Yanagisawa, and C. E. Gariepy Extrarenal ETB Plays a Significant Role in Controlling Cardiovascular Responses to High Dietary Sodium in Rats Hypertension, May 1, 2005; 45(5): 940 - 946. [Abstract] [Full Text] [PDF]

				D. M. Pollock Endothelin, Angiotensin, and Oxidative Stress in Hypertension Hypertension, April 1, 2005; 45(4): 477 - 480. [Full Text] [PDF]

				A. A. Elmarakby, E. D. Loomis, J. S. Pollock, and D. M. Pollock NADPH Oxidase Inhibition Attenuates Oxidative Stress but Not Hypertension Produced by Chronic ET-1 Hypertension, February 1, 2005; 45(2): 283 - 287. [Abstract] [Full Text] [PDF]

				J. M. Williams, J. S. Pollock, and D. M. Pollock Arterial Pressure Response to the Antioxidant Tempol and ETB Receptor Blockade in Rats on a High-Salt Diet Hypertension, November 1, 2004; 44(5): 770 - 775. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 41/6/1359    most recent 01.HYP.0000070958.39174.7Ev1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vassileva, I. Articles by Pollock, D. M. Search for Related Content PubMed PubMed Citation Articles by Vassileva, I. Articles by Pollock, D. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB SODIUM CHLORIDE Related Collections Cardio-renal physiology/pathophysiology Hypertension - basic studies Endothelium/vascular type/nitric oxide