(Hypertension. 1996;27:643-648.)
© 1996 American Heart Association, Inc.
Articles |
Renal Response to L-Arginine in Salt-Sensitive Patients With Essential Hypertension
From the First Department of Internal Medicine and the Department of Clinical Laboratory Medicine (T.O.), Hiroshima University School of Medicine, Hiroshima, Japan.
Correspondence to Yukihito Higashi, MD, First Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
Abstract This study examined whether disturbances in nitric oxide formation contribute to renal dysfunction in salt-sensitive essential hypertensive patients. We evaluated the effects of intravenous administration of L-arginine (500 mg/kg given over 30 minutes) on systemic and renal hemodynamics in 23 patients with mild essential hypertension during 1 week of a low NaCl diet (50 mmol/d) followed by 1 week of a high NaCl diet (340 mmol/d). Patients were classified as salt sensitive (n=10) or salt resistant (n=13) based on salt-induced changes in their blood pressures. Salt loading increased renal vascular resistance but not renal plasma flow in salt-sensitive patients. The L-arginine–induced renovascular relaxation was significantly reduced by a high NaCl diet (renal vascular resistance: low NaCl -12.4±2.3% versus high NaCl -7.1±1.8%, P<.001) in salt-sensitive patients, whereas it was unchanged in salt-resistant patients. The increase in plasma cGMP in response to L-arginine was also reduced by a high NaCl diet in the salt-sensitive patients (low NaCl 49±7% versus high NaCl 36±8%, P<.05) but not in the salt-resistant patients (low NaCl 51±6 versus high NaCl 58±6%). These findings suggest that NaCl loading in salt-sensitive patients with mild essential hypertension reduces the ability of L-arginine to produce nitric oxide in the endothelium of the renal vasculature.
Key Words: L-arginine • nitric oxide • cyclic GMP • hypertension, sodium-dependent • blood pressure • renal circulation
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
There is evidence that endothelium-derived relaxing factor–nitric oxide plays a vital role in the regulation of systemic and renal hemodynamics.1 2 3 4 5 Nitric oxide, which is produced from L-arginine in the presence of nitric oxide synthase in the endothelium, stimulates cytosolic guanylate cyclase and increases guanosine 3',5'-cGMP content in vascular smooth muscle cells, resulting in relaxation of vascular tone.6 7 Several investigators have reported a disturbance of endothelium-dependent vascular relaxation in essential hypertension in patients and in animals with experimentally induced hypertension.8 9 10 11 We have reported that even patients with mild essential hypertension demonstrate an impaired endothelium-dependent renal vascular relaxation.4 These findings suggest that abnormalities in endothelium-dependent vasodilation may be involved in the pathogenesis of hypertension.
NaCl has been established as an important factor in the development of hypertension.12 13 However, excessive amounts of NaCl do not always elevate blood pressure, since the pressure response to NaCl loading varies among individuals.14 The mechanism underlying these differences in salt sensitivity has not been fully clarified. There is limited information regarding the association between endothelium-dependent vasodilation and blood pressure response to changes in dietary NaCl intake. In recent studies, endothelial dysfunction was augmented by NaCl loading in experimental models of hypertension.10 11 Hypertension induced by a high NaCl diet in Dahl salt-sensitive rats was prevented by the prolonged administration of L-arginine.10 To the best of our knowledge, there is no information regarding the in vivo effects of NaCl diet on endothelial function in humans.
This study examines whether endothelium-dependent nitric oxide–mediated regulation of renal vascular tone is affected by dietary NaCl. We examined the effects of changes in dietary NaCl on the effects of intravenous infusion of L-arginine on renal hemodynamic function.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Subjects
We studied 23 Japanese inpatients with mild to moderate essential hypertension (16 men and 7 women; mean age, 54±4 years). Hypertension was defined as a systolic blood pressure >160 mm Hg and/or a diastolic blood pressure >95 mm Hg, in sitting position, on at least three different occasions. Blood pressure measurements were obtained in the outpatient clinic of Hiroshima University School of Medicine. Patients with secondary forms of hypertension were excluded by appropriate clinical and biochemical examinations. None of the patients had a history of cardiovascular or cerebrovascular disease, hypercholesterolemia, diabetes mellitus, liver disease, or renal disease. The study protocol was approved by the ethics committee of the First Department of Internal Medicine, Hiroshima University School of Medicine. Informed consent for participation was obtained from all subjects.
Study Protocol
Patients did not take any antihypertensive
agents for at
least 4 weeks before the study. One week before the study, hypertensive
subjects were initially kept on a regular diet that contained 170 mmol
NaCl per day to allow a stabilization of the systemic sodium balance
and blood pressures. Essential hypertensive patients were subsequently
placed on a low NaCl diet (50 mmol/d) for 1 week, followed by a high
NaCl diet (340 mmol/d) for 1 week. The high NaCl diet was achieved by
the addition of Slow-Sodium tablets (10 mmol NaCl per tablet; Mission
Pharmaceutical Co) to the diet. Throughout the study, the subjects
ingested a constant amount of potassium (100 mmol/d) and calcium (40
mmol/d). Their caloric intake was 40 cal/kg per day. All inpatients
were given dietary meals prepared in the Hiroshima University Hospital
kitchen. Rigid compliance to the diet was confirmed by measuring the
24-hour urinary excretion of sodium, chloride and potassium throughout
the study. We used 50 and 340 mmol NaCl per day because they are actual
and ordinary. One hundred and seventy mmol NaCl per day is the average
NaCl intake of our inhabitants. In ordinary life, 50 mmol/d is the
lowest NaCl intake encountered. Dietary NaCl intake >340 mmol/d can be
seen in 
10% of our outpatients on a free diet.
The L-arginine infusion study began at 8:30 AM. On the seventh morning of each NaCl dietary period, subjects fasted overnight for at least 12 hours and were kept in a supine position in a quiet, dark, air-conditioned room maintained at a constant temperature (22°C to 25°C) throughout the study. A 19-gauge polyethylene catheter (Terumo Co) was inserted into the right antecubital vein for the infusion of PAH, inulin, and L-arginine. A second catheter was inserted into the left antecubital vein to obtain blood samples. After a 30-minute rest period, initial doses of PAH (8.0 mg/kg) and inulin (16 mg/kg) were infused as a bolus. PAH and inulin were subsequently infused at a constant rate of 12 and 20 mg/min, respectively, with a syringe pump (Terfusion; Terumo Co) throughout the study.15 16 Sixty minutes after the PAH and inulin infusions began, L-arginine (500 mg/kg) was administered over 30 minutes with the use of an infusion pump (PEI-1000; Pal Medical Co). A 30-minute recovery period followed the end of the L-arginine infusion. Blood pressure and heart rate measurements were obtained every minute by attaching a TM2420 monitor (AND Co) to the upper left arm. Mean blood pressure was calculated as the diastolic pressure plus one third of the pulse pressure. Blood samples were obtained to determine serum concentrations of PAH, inulin, and plasma cGMP at 0 minutes and at 15, 30, and 60 minutes after the start of L-arginine administration. Baseline fasting serum concentrations of total cholesterol, creatinine, glucose, electrolytes, PRA, Ang II, and PAC were obtained at 0 minutes.
Drugs
The L-arginine used for intravenous
administration was L–arginine hydrochloride
(Morishita/Ruseru Pharmaceutical Co). The administered inulin was
Inutest (Laevosan-Gesellschaft); PAH was from Daiichi Pharmaceutical
Co.
Analytical Methods
Salt sensitivity was defined by the
percent change in mean
blood pressure resulting from the low NaCl diet (50 mmol/d) to the high
NaCl diet (340 mmol/d). Patients were defined as SS when the change in
mean blood pressure by NaCl loading was 10% or greater and as SR when
the change was less than 10%.
Routine chemical methods were used to determine serum concentrations of total cholesterol, creatinine, glucose, and electrolytes, and urinary electrolytes. PRA (Gamma coat PRA kit, Special Reference Laboratory), Ang II (anti–angiotensin II antibody, SRL Co), and PAC (SPAC-S aldosterone kit, Daiichi Radioisotope Laboratory Ltd) were measured by radioimmunoassay. Plasma cGMP levels were measured by radioimmunoassay with the use of cGMP kits (Yamasa Shoyu Co). RPF was determined on the basis of the clearance of PAH. Serum PAH concentration was analyzed by spectrophotometry. GFR was determined on the basis of the clearance of inulin.17 Serum inulin concentration was analyzed by the anthrone method.18 Renal blood flow was calculated with the use of PAH clearance and hematocrit values. RVR was calculated as the mean blood pressure divided by renal blood flow, and FF was calculated as GFR divided by RPF. RPF, GFR, and RVR were normalized to body surface area divided by 1.48 m2 (1.48 m2 being the average body surface area of the Japanese population).
Statistical Analysis
Results are presented as
mean±SEM. Baseline
parameters during the low NaCl and the high NaCl diets were
compared with the Student's paired t test. Differences
between SS and SR patients were compared using Student's unpaired
t test, and their responses to L-arginine were
compared using ANOVA for repeated measures followed by Scheffé's
F test. Values of P<.05 were considered
statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Changes in blood pressure after NaCl loading indicated that 10 patients were SS (6 men and 4 women; mean age, 55±4 years) and 13 were SR (10 men and 3 women; mean age, 52±4 years). There were no significant differences in age, sex, or body mass index between the two groups. During the administration of a regular diet containing 170 mmol NaCl per day, the baseline values for parameters were similar in the SS and SR patients, as shown in the Table
.
|
Effects of Dietary NaCl Intake on Baseline Clinical Characteristics
in SS and SR Patients
The baseline values for the parameters measured
in the
SS and SR patients on low and high NaCl diets are summarized in the
Table
. During a low NaCl dietary period, there were no
significant
differences in parameters between the SS and the SR
patients, except in the case of PRA, which was higher in the SR
patients than in the SS patients (P<.05). After patients
switched from a low NaCl diet to a high NaCl diet, body weight
(P<.01) and urinary sodium excretion (P<.001)
increased significantly, and the indexes of the
renin-angiotensin-aldosterone axis,
such as PRA (P<.01), PAC (P<.01), and Ang II
(P<.01), were significantly depressed in both the SS and SR
patients. The responses of these parameters to dietary NaCl
were similar in the two groups, except for PRA. Mean blood pressure and
RVR were significantly increased by an NaCl loading in the SS group of
essential hypertensive patients (P<.01) but unchanged in
the SR group. The RPF was significantly increased (P<.05)
and FF was decreased (P<.05) in the SR patients, but they
were not significantly changed in SS patients. The increase in RVR
induced by high NaCl intake was greater in SS patients, but the high
NaCl–induced increase in RPF was greater in the SR patients. The
other parameters including plasma cGMP concentration did
not change by a NaCl loading.
Effects of L-Arginine Infusion on Systemic
Hemodynamics
Fig 1 shows the percent change in mean
blood
pressure and heart rate above baseline levels during the infusion of
L-arginine in SS and SR patients on low and high NaCl
diets. After the start of L-arginine infusion, mean blood
pressure promptly decreased and reached a plateau at 20 minutes in both
groups on each diet. A prompt return to baseline levels occurred after
L-arginine infusion in both groups. The change in dietary
NaCl intake did not induce any significant change in blood pressure
response to L-arginine in either group. The groups did not
differ with respect to the time course of percent change in mean blood
pressure on either NaCl diet. The administration of
L-arginine increased the heart rate in both groups. The
heart rate gradually returned to baseline during the resting period.
There was no significant difference between the two groups in the time
course of changes in heart rate.
|
) and high (
) NaCl diets in SS and SR patients
with essential hypertension. The responses of mean blood pressure and
heart rate to L-arginine were similar in the two groups.
Results are presented as mean±SEM. Probability value refers to
the comparison of time-course curves with the use of ANOVA for
repeated measures.
Effects of L-Arginine Infusion on Renal
Hemodynamics
Intravenous infusion of L-arginine
produces renal vasodilation, resulting in an increase in RPF and
decreases in RVR and FF. L-arginine infusion did not affect
GFR in the SS or the SR patient group on either diet.
L-arginine–induced increases in RPF were similar in SS
patients (10.1±1.2% versus 10.4±1.1%) and SR patients
(11.0±1.3%
versus 10.7±1.2%) during the regular and low NaCl dietary periods.
Whereas an increase in RPF in response to L-arginine was
attenuated by NaCl loading in SS patients, the responses were not
significantly altered by NaCl loading in SR patients. Thus, during the
high NaCl dietary period, SS patients exhibited a significantly lower
increase in RPF than SR patients (5.8±1.2% versus 12.3±1.3%,
P<.001), as shown in Fig 2 (top). The
decrease in RVR in response to L-arginine infusion was also
similar in the SS (-11.7±2.2% and -12.2±2.3%) and
the
SR (-12.8±2.1% and -12.5±2.0%) patients during the
regular and low NaCl dietary periods. After an NaCl load, the
L-arginine–induced decrease in RVR was lessened in SS
patients but unchanged in SR patients. Thus, the decrease in RVR by
L-arginine on the high NaCl diet was significantly smaller
in SS patients than in SR patients (-7.1±1.8% versus
-13.2±2.1%, P<.001), as shown in Fig 2
(bottom).
The L-arginine–induced decrease in FF was attenuated
by NaCl loading in SS patients but was unaffected in SR patients. Thus,
during NaCl loading, the decrease in FF was significantly lower in the
SS patients than in SR patients (-1.7±1.2% versus
-7.3±1.4%, P<.01), whereas the change in FF was
similar in the two groups during NaCl depletion.
|
) and SR patients
on high NaCl (
) diets. Results are
presented as mean±SEM. Probability values refer to the
comparison of time-course curves with the use of ANOVA for repeated
measures.
Effects of L-Arginine Infusion on Plasma cGMP
Concentration
We measured the plasma cGMP concentration as an
indicator of
nitric oxide production. Baseline plasma cGMP levels were
similar in the SS and SR patients on the regular, low, and high NaCl
diets (Table). The effects of NaCl intake on the
L-arginine–induced increases in plasma cGMP are shown
in Fig 3. The L-arginine–induced
increase in cGMP was similar in the SS patients (48±8% and
49±7%)
and the SR patients (53±7% and 51±6%) during the regular and low
NaCl diets. Whereas the increase in cGMP response to
L-arginine was reduced by NaCl loading in SS patients, the
responses in SR patients were similar in both diets. Thus, during the
high NaCl diet, the SS patients showed a significantly lower increase
in cGMP than did the SR patients (36±8% versus 58±6%,
P<.05).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Recent studies indicate that alteration of the nitric oxide pathway may be involved in the pathogenesis of hypertension in association with an endothelial dysfunction.8 19 20 Several animal models of hypertension have demonstrated a reduction of nitric oxide release in the endothelium.21 22 In patients with essential hypertension, the endothelium-dependent vasodilation induced by acetylcholine or bradykinin is impaired in coronary and brachial arteries.8 9 23 We recently reported that the endothelium-dependent renovascular relaxation is also impaired even in patients with mild essential hypertension who have normal RPF and GFR and lack objective signs of end-organ damage compared with healthy subjects.4 Thus, our findings suggest that changes in renal endothelial function may be a cause rather than a consequence of hypertension.
Epidemiological and clinical studies have confirmed that the excessive intake of NaCl is involved in the pathogenesis of hypertension.12 24 25 However, the mechanism by which excess sodium intake affects blood pressure in humans is not fully clarified. The kidney, because of its direct role in modulating sodium balance, is one of the primary determinants of NaCl sensitivity. Indeed, the primacy of the kidney in the development of NaCl-induced hypertension has been confirmed in a series of transplant experiments.26 However, relatively little attention has focused on the role of renal hemodynamic modification in the salt sensitivity of blood pressure.24 27 The present study demonstrated substantial differences between SS and SR patients with "Japanese essential hypertension" in terms of the adaptation of renal hemodynamics to the high NaCl diet. After NaCl loading, RVR was increased and RPF was unchanged in SS patients, whereas in SR patients RVR did not change but RPF was increased. A disturbed response of renal hemodynamics to NaCl intake also has been reported in black salt-sensitive patients with essential hypertension.27 Thus, the ability of NaCl loading to elevate the RVR may contribute to its pressor effect. Several investigators have reported an increase in forearm vascular resistance in salt-sensitive patients.28 A widespread increase in vascular resistance therefore may be a common characteristic of NaCl-induced hypertension.
The difference in the response of the renal circulation to an NaCl load between the SS and SR patients may result from different modification in endothelium-dependent vasodilation, as demonstrated in rats with NaCl-induced hypertension.10 11 In the present study, the intravenous administration of L-arginine similarly increased the RPF and decreased the RVR in both the SS and SR patients during a low NaCl diet. While the increase in RPF and the reduction in RVR in response to L-arginine were attenuated by NaCl loading in SS patients, these responses were similar in both diets in SR patients. These findings suggest that an impairment of the endothelium-dependent renovascular relaxation is increased by NaCl loading in SS patients but is unaffected by the change in dietary NaCl intake in SR patients. Thus, the reduction in endothelium-dependent vasodilation by NaCl loading may be important in elevating the RVR and increasing the blood pressure in SS patients.
Lahera et al29 have suggested that a deficient production of nitric oxide may cause salt-sensitive hypertension. In SS patients, reduced release of nitric oxide from endothelial cells may influence renal hemodynamics under the basal condition, as well as with stimuli. In the present study, we indicated that L-arginine–induced increases in plasma cGMP, a biological marker of nitric oxide production, were attenuated in SS patients on a high NaCl diet. Thus, reduced nitric oxide production may be the mechanism by which the renovascular relaxation response to L-arginine infusion is attenuated in SS patients with essential hypertension on a high NaCl diet.
In addition to the reduction in the endothelium-dependent renal vasodilation, a decreased response of the PRA to changes in dietary NaCl intake was detected in SS patients. This finding reconfirms those reported in our previous study30 and may be attributed to the possible interaction between the L-arginine–nitric oxide pathway and the renin-angiotensin system. Other than an inadequate suppression of the renin-angiotensin axis, our research has demonstrated an intracellular accumulation of sodium and calcium and an apparent hereditary component of hypertension as the mechanisms underlying the elevation in blood pressure in response to NaCl load.31 32 Considering the heterogeneity of the pathogenesis of essential hypertension, a single factor cannot independently determine NaCl sensitivity. Further studies are required to clarify the interrelationships between NaCl-induced modification of endothelium-dependent renal vasodilation and other factors contributing to NaCl sensitivity.
In conclusion, in the present study RVR increased but RPF did not change in response to a high NaCl diet in SS patients, whereas in SR patients RVR did not change but RPF increased. In addition, this is the first report to demonstrate the attenuation of endothelium-dependent renal vascular relaxation in response to high NaCl intake in SS patients with essential hypertension. During high NaCl intake, the L-arginine–induced increase in cGMP production was decreased in SS patients compared with SR patients. The different modifications in L-arginine–nitric oxide–cGMP pathway in renal circulation during NaCl repletion may play a role in altering the NaCl sensitivity of the blood pressure in patients with essential hypertension.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
This study was supported in part by a Grant-in-Aid for Scientific Research (A, No. 06304028 and C. No. 06672293) from the Ministry of Education, Science, and Culture of Japan and a Foundation for Total Health Promotion grant (1992). The authors thank Dr Ryoji Ozono for technical advice, Sumiko Nakamura for preparation of the diets, and Yuko Omura for her secretarial assistance.
Received September 20, 1995; first decision October 31, 1995; accepted November 20, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Vanhoutte PM. Endothelium and control of vascular function. Hypertension.. 1989;13:658-667.
2.
Rees DD, Palmer RMJ, Moncada S. Role of
endothelium-derived nitric oxide in the regulation
of blood pressure. Proc Natl Acad Sci U S A.. 1989;86:3375-3378.
3. Raij L. Nitric oxide and the kidney. Circulation. 1993;87(suppl V):V-26-V-29.
4.
Higashi Y, Oshima T, Ozono R, Watanabe M, Matsuura H,
Kajiyama G. Effects of L-arginine infusion on renal
hemodynamics in patients with mild essential
hypertension. Hypertension.. 1995;25:898-902.
5. Higashi Y, Oshima T, Ono N, Hiraga H, Yoshimura M, Watanabe M, Matsuura H, Kambe M, Kajiyama G. Intravenous administration of L-arginine inhibits angiotensin-converting enzyme in humans. J Clin Endocrinol Metab.. 1995;80:2198-2202. [Abstract]
6.
Arnold WP, Mittal CK, Katuki S, Murad F. Nitric
oxide activates guanylate cyclase and increases
guanosine 3',5'-cyclic monophosphate levels in various tissue
preparations. Proc Natl Acad Sci U S A.. 1977;74:3203-3206.
7. Palmer RMJ, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature.. 1988;333:664-666. [Medline] [Order article via Infotrieve]
8. 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]
9.
Treasure CB, Klein JL, Vita JA, Manoukian SV, Renwick
GH, Selwyn AP, Ganz P, Alexander RW. Hypertension and left
ventricular hypertrophy are associated with
impaired endothelium-mediated relaxation in human
coronary resistance vessels.
Circulation. 1993;87:86-93.
10. Chen PY, Sanders PW. L-arginine abrogates salt-sensitive hypertension in Dahl/Rapp rats. J Clin Invest.. 1991;88:1559-1567.
11.
Patel A, Layne S, Watts D, Kirchner KA.
L-arginine administration normalizes pressure natriuresis
in hypertensive Dahl rats. Hypertension.. 1993;22:863-869.
12. INTERSALT Cooperative Research Group. INTERSALT-an international study of electrolyte excretion and blood pressure: results for 24 hour urinary sodium and potassium excretion. Br Med J.. 1988;297:319-354.
13. Campese VM, Romoff MS, Levitan D, Saglikes Y, Friedler RM, Masry SG. Abnormal relationship between Na+ intake and sympathetic nervous system activity in salt-sensitive patients with essential hypertension. Kidney Int.. 1982;21:371-378. [Medline] [Order article via Infotrieve]
14.
Oshima T, Matsuura H, Kido K, Kajiyama G. Role
of cellular calcium in salt sensitivity of patients with essential
hypertension. Hypertension.. 1988;11:703-707.
15. Cole BR, Gianiacomo J, Ingelfinger JR, Robson AM. Measurement of renal function without urine collection. N Engl J Med.. 1972;22:1109-1114.
16. Schnurr R, Lahme W, Kuppers H. Measurement of renal clearance of inulin and PAH in the steady state without urine collection. Clin Nephrol.. 1980;13:26-29.[Medline] [Order article via Infotrieve]
17. Friedman SM, Polley JR, Friedman CL. The clearance of inulin and sodium p-amino hippurate in the rat. Am J Physiol. 1947;150:340-352.
18. Davidson W, Sackner MA. Simplification of the anthrone method for the determination of inulin in clearance studies. J Lab Clin Med.. 1963;62:351-356. [Medline] [Order article via Infotrieve]
19. Vallance P, Collier J, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet.. 1989;2:997-1000. [Medline] [Order article via Infotrieve]
20. Vane JR, Anggard EE, Botting RM. Regulatory function of the vascular endothelium. N Engl J Med.. 1990;323:27-36. [Medline] [Order article via Infotrieve]
21.
Salazar FJ, Pinilla JM, Lopes F, Romero JC, Quesada
T. Renal effects of prolonged synthesis inhibition of
endothelium-derived nitric oxide.
Hypertension.. 1992;20:113-117.
22.
Sigmon DH, Carretero OA, Beierwaltes WH.
Angiotensin dependence of
endothelium-mediated renal
hemodynamics. Hypertension.. 1992;20:643-650.
23. Brush JE Jr, Cannon RO III, Schenke WH, Bonow RO, Leon MB, Maron BJ, Epstein SE. Angina due to coronary microvascular disease in hypertensive patients without left ventricular hypertrophy. N Engl J Med.. 1988;319:1302-1307. [Abstract]
24. Campese VM. Effects of calcium antagonists on deranged modulation of the renal function curve in salt-sensitive patients with essential hypertension. Am J Cardiol.. 1988;62:85G-91G. [Medline] [Order article via Infotrieve]
25. Kawasaki T, Delea CS, Bartter FC, Smith H. The effects of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension. Am J Med.. 1978;64:193-198.[Medline] [Order article via Infotrieve]
26.
Dahl KH, Heine M. Primary role of renal
homografts in setting chronic blood pressure and levels in
rats. Circ Res.. 1975;36:692-696.
27.
Campese VM, Parise M, Karubian F, Bigazzi R.
Abnormal renal hemodynamics in black salt-sensitive
patients with hypertension. Hypertension.. 1991;18:805-812.
28. Sullivan JM. Salt sensitivity: definition, conception, methodology, and long-term issues. Hypertension. 1991;17(suppl I):I-61-I-68.
29. Lahera V, Salazar J, Salom MG, Carlos RJ. Deficient production of nitric oxide induces volume-dependent hypertension. J Hypertens. 1992;10(suppl 7):S173-S177.
30.
Oshima T, Matsuura H, Kido K, Matsumoto K, Fujii H,
Masaoka S, Okamoto M, Tsuchioka Y, Kajiyama G, Tsubokura T.
Intralymphocytic sodium and free calcium and plasma renin in essential
hypertension. Hypertension.. 1988;12:26-31.
31. Oshima T, Matsuura H, Kido K, Matsumoto K, Shingu T, Otsuki T, Kajiyama G. Factors determining sodium chloride sensitivity of patients with essential hypertension: evaluation by multivariate analysis. J Hypertens.. 1989;7:223-227. [Medline] [Order article via Infotrieve]
32. Oshima T, Matsuura H, Ishibashi K, Kainouchi M, Ishida T, Ozono R, Fujii H, Kajiyama G. Familial influence upon NaCl sensitivity in patients with essential hypertension. J Hypertens.. 1992;10:1089-1094.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  E. Ritz How Little Aldosterone is Able to Raise Blood Pressure? Clin. J. Am. Soc. Nephrol., April 1, 2009; 4(4): 703 - 710. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Li, J. White, L. Guo, X. Zhao, J. Wang, E. J. Smart, and X.-A. Li Salt Inactivates Endothelial Nitric Oxide Synthase in Endothelial Cells J. Nutr., March 1, 2009; 139(3): 447 - 451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Coylewright, J. F. Reckelhoff, and P. Ouyang Menopause and Hypertension: An Age-Old Debate Hypertension, April 1, 2008; 51(4): 952 - 959. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Oberleithner, C. Riethmuller, H. Schillers, G. A. MacGregor, H. E. de Wardener, and M. Hausberg Plasma sodium stiffens vascular endothelium and reduces nitric oxide release PNAS, October 9, 2007; 104(41): 16281 - 16286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Wieczorek-Surdacka, A. Surdacki, S. M. Bode-Boger, B. Schubert, and W. Sulowicz Elevated plasma asymmetric dimethyl-L-arginine in a patient with Gordon syndrome Nephrol. Dial. Transplant., January 1, 2007; 22(1): 268 - 271. [Full Text] [PDF]
|
|
|
|
|
|
Y. Fang, J.-J. Mu, L.-C. He, S.-C. Wang, and Z.-Q. Liu Salt Loading on Plasma Asymmetrical Dimethylarginine and the Protective Role of Potassium Supplement in Normotensive Salt-Sensitive Asians Hypertension, October 1, 2006; 48(4): 724 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. West, A. Likos-Krick, P. Brown, and F. Mariotti Oral L-Arginine Improves Hemodynamic Responses to Stress and Reduces Plasma Homocysteine in Hypercholesterolemic Men J. Nutr., February 1, 2005; 135(2): 212 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bello, C. Caramelo, N. Martell, J. M. Alcazar, J. Gonzalez, M. D. Lopez, L. M. Ruilope, F. R. Gonzalez, A. M. Rovira, R. Gazapo, et al. Impairment of Renal Vasodilation With L-Arginine Is Related to More Severe Disease in Untreated Hypertensive Patients Hypertension, October 1, 2001; 38(4): 907 - 912. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-L. Ma, F. Gao, A. H. Nelson, B. L. Lopez, T. A. Christopher, T.-L. Yue, and F. C. Barone Oxidative Inactivation of Nitric Oxide and Endothelial Dysfunction in Stroke-Prone Spontaneous Hypertensive Rats J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 879 - 885. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. PERINOTTO, A. BIGGI, N. CARRA, A. ORRICO, G. VALMADRE, P. DALL'AGLIO, A. NOVARINI, and A. MONTANARI Angiotensin II and Prostaglandin Interactions on Systemic and Renal Effects of L-NAME in Humans J. Am. Soc. Nephrol., August 1, 2001; 12(8): 1706 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-T. DIJKHORST-OEI, P. BOER, T. J. RABELINK, and H. A. KOOMANS Nitric Oxide Synthesis Inhibition Does Not Impair Water Immersion-Induced Renal Vasodilation in Humans J. Am. Soc. Nephrol., July 1, 2000; 11(7): 1293 - 1302. [Abstract] [Full Text]
|
|
|
|
 |
|
 N. Fujiwara, T. Osanai, T. Kamada, T. Katoh, K. Takahashi, and K. Okumura Study on the Relationship Between Plasma Nitrite and Nitrate Level and Salt Sensitivity in Human Hypertension : Modulation of Nitric Oxide Synthesis by Salt Intake Circulation, February 29, 2000; 101(8): 856 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Kone and S. Higham Nitric oxide inhibits transcription of the Na+-K+-ATPase alpha 1-subunit gene in an MTAL cell line Am J Physiol Renal Physiol, April 1, 1999; 276(4): F614 - F621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Bech, C. B. Nielsen, P. Ivarsen, K. T. Jensen, and E. B. Pedersen Dietary sodium affects systemic and renal hemodynamic response to NO inhibition in healthy humans Am J Physiol Renal Physiol, May 1, 1998; 274(5): F914 - F923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Higashi, T. Oshima, R. Ozono, Y. Nakano, H. Matsuura, M. Kambe, and G. Kajiyama Nocturnal Decline in Blood Pressure Is Attenuated by NaCl Loading in Salt-Sensitive Patients With Essential Hypertension : Noninvasive 24-Hour Ambulatory Blood Pressure Monitoring Hypertension, August 1, 1997; 30(2): 163 - 167. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Higashi, T. Oshima, R. Ozono, H. Matsuura, and G. Kajiyama Aging and Severity of Hypertension Attenuate Endothelium-Dependent Renal Vascular Relaxation in Humans Hypertension, August 1, 1997; 30(2): 252 - 258. [Abstract] [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||