Renal 20-HETE inhibition attenuates changes in renal hemodynamics induced by l-NAME treatment in pregnant rats

2005 ◽  
Vol 289 (5) ◽  
pp. F1116-F1122 ◽  
Author(s):  
Hui Huang ◽  
Yiqiang Zhou ◽  
Venugopal T. Raju ◽  
Juan Du ◽  
Hsin-Hsin Chang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Combined Treatment ◽  
Renal Hemodynamics ◽  
Female Rats ◽  
Control Group ◽  
Pregnant Rats ◽  
Functional Changes ◽  
No Inhibition ◽  
Renal Vascular

We previously reported that inhibition of nitric oxide (NO) synthesis by N-nitro-l-arginine methyl ester (l-NAME) during late pregnancy leads to increased production of renal vascular 20-hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P-450 (CYP) 4A-derived vasoconstrictor, in pregnant rats. However, the effect of upregulation of vascular 20-HETE production on renal function after NO inhibition is not known. To test the hypothesis that increased gestational vascular 20-HETE synthesis after NO inhibition is involved in mediating blood pressure and renal functional changes, we first determined the IC50 value of the effect of nitroprusside (SNP), a NO donor, on renal 20-HETE production in cortical microsomes. We then divided pregnant rats and age-matched virgin rats into a vehicle control group, an l-NAME treatment group (0.25 mg/ml in drinking water), and a group treated with l-NAME plus N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS; CYP4A-selective inhibitor, 10 mg·kg−1·day−1 iv). After 4 days of treatment, we measured blood pressure, renal blood flow (RBF), renal vascular resistance (RVR), and glomerular filtration rate (GFR) in each group. The addition of SNP (IC50 = 22 μM) decreased renal cortical 20-HETE production. In pregnant rats, l-NAME treatment led to significantly higher mean arterial pressure (MAP) and RVR, and lower RBF and GFR. Combined treatment with DDMS and l-NAME significantly attenuated the increases in MAP and RVR and the decrease in GFR, but not the reduction in RBF induced by l-NAME treatment. l-NAME and l-NAME plus DDMS had no significant impact on renal hemodynamics in virgin rats. In addition, chronic treatment with DDMS selectively inhibited cortical 20-HETE production without a significant effect on CYP4A expression in l-NAME-treated pregnant rats. In conclusion, NO effectively inhibits renal cortical microsomal 20-HETE production in female rats. In pregnant rats, the augmentation of renal 20-HETE production after NO inhibition is associated with increased MAP and RVR, whereas decreased GFR is negated by treatment of a selective and competitive CYP4A inhibitor. These results demonstrate that the interaction between renal 20-HETE and NO is important in the regulation of renal function and blood pressure in pregnant rats.

Age-related changes in renal hemodynamics in female rats: role of multiple pregnancy and NO

1997 ◽  
Vol 272 (6) ◽  
pp. R1985-R1989 ◽  
Author(s):  
J. F. Reckelhoff
Keyword(s):  
Renal Function ◽  
Renal Plasma Flow ◽  
Multiple Pregnancy ◽  
Renal Hemodynamics ◽  
Female Rats ◽  
No Production ◽  
Renal Vasculature ◽  
Pregnant Rats ◽  
Age Related ◽  
Renal Vascular

The objective of the present study was to evaluate 1) the effect of multiple pregnancy and aging on renal function and 2) the effect of NO inhibition on renal function in aged virgin and multiply pregnant rats. Renal hemodynamics were measured in the presence or absence of chronic (2 wk) NO synthase inhibition (nitro-L-arginine methyl ester, L-NAME) in young virgins (YV, 3-4 mo), old virgins (OV, 17-18 mo), and old retired breeders (ORB, 17-18 mo) that had sustained eight to nine pregnancies and lactations. Blood pressure was not different between control YV and OV. Glomerular filtration rate (GFR), renal plasma flow (RPF), and renal vascular resistance (RVR) were similar in OV and control YV. In contrast, the renal vasculature of ORB was more vasoconstricted in ORB than in YV or OV:GFR was decreased by 35% and RVR was higher than in YV or OV. With L-NAME there were similar increases in arterial pressure in all rats. In control YV, L-NAME had no effect on GFR, decreased RPF by 20%, and increased RVR by twofold. In OV, L-NAME decreased GFR by 30% and RPF by 60% and increased RVR by 3.3-fold. In ORB, L-NAME had no effect on GFR, decreased RPF by 30%, and increased RVR by 1.8-fold. These data suggest that the renal vasculature of ORB is vasoconstricted and that the mechanism may be due to a decrease in NO production.

scholarly journals Altered vascular contractility in adult female rats with hypertension programmed by prenatal glucocorticoid exposure

2006 ◽  
Vol 188 (3) ◽  
pp. 435-442 ◽  
Author(s):  
P W F Hadoke ◽  
R S Lindsay ◽  
J R Seckl ◽  
B R Walker ◽  
C J Kenyon
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Adult Female ◽  
Vascular Function ◽  
Mesenteric Arteries ◽  
Female Rats ◽  
Control Group ◽  
Pregnant Rats ◽  
Vascular Contractility

Excessive exposure to glucocorticoids during gestation reduces birth weight and induces permanent hypertension in adulthood. The mechanisms underlying this programmed elevation of blood pressure have not been established. We hypothesised that prenatal glucocorticoid exposure may lead to vascular dysfunction in adulthood. Pregnant rats received dexamethasone (Dex) (100 μg/kg, s.c.) or vehicle (control) daily throughout pregnancy. Blood pressure was elevated (students t-test, unpaired; P < 0.05) in adult female offspring (aged 12–16 weeks) of Dex-treated mothers (148.0 ± 3.6 mmHg, n=10) compared with the control group (138.0 ± 2.5 mmHg, n=8). Vascular responsiveness in aortae and mesenteric arteries was differentially affected by prenatal Dex: aortae were less responsive to angiotensin II, whereas mesenteric arteries were more responsive to norepinephrine, vasopressin and potassium (mesenteric arteries respond poorly to angiotensin II in vitro). Acetylcholine-mediated, endothelium-dependent relaxation was similar in both groups. Prenatal exposure to Dex had no effect on blood pressure or aldosterone response to acute (15 min, i.v.) infusion of angiotensin II (75 ng/kg per min). In contrast, chronic (2-week, s.c.) infusion of angiotensin II (100 ng/kg per min) produced a greater elevation (P < 0.05) of blood pressure in Dex-treated rats (150.0 ± 3.6 mmHg) than in controls (135.3 ± 5.4 mmHg), and aldosterone levels were higher in Dex-treated animals. There was no angiotensin II-induced medial hypertrophy/hyperplasia in mesenteric arteries from Dex-treated rats. These results indicate that vascular function is altered in a region-specific manner in rats with glucocorticoid-programmed hypertension. Despite a striking increase in mesenteric artery contraction in Dex-treated rats, in vivo studies suggest that abnormalities of the renin-angiotensin-aldosterone system, rather than enhanced vascular contractility, may be responsible for the elevation of blood pressure in these animals.

P0117DOSE ESCALATING TOXICOLOGY STUDY OF ELP-VEGF, A NOVEL BIOLOGIC FOR RENAL THERAPEUTIC ANGIOGENESIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gene Bidwell ◽  
Jamarius Waller ◽  
Jason Engel ◽  
Alejandro Chade
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Body Weight ◽  
Therapeutic Dose ◽  
Therapeutic Angiogenesis ◽  
Female Rats ◽  
Vascular Density ◽  
Therapeutic Doses ◽  
Renal Vascular ◽  
Dose Escalating

Abstract Background and Aims Chronic renal disease, irrespective of the etiology, is hallmarked by renal microvascular rarefaction. This rarefaction is associated with a reduced bioavailability of the pro-angiogenic cytokine vascular endothelial growth factor (VEGF). Recently, we developed a therapeutic intervention for ischemic renal conditions using therapeutic angiogenesis – supplementing renal VEGF levels. This was achieved by administration of a biopolymer-stabilized form of VEGF using a fusion protein between human VEGF-A121 and an elastin-like polypeptide carrier protein (ELP-VEGF). ELP-VEGF induced microvascular remodeling and increased microvascular density when administered intra-renally in swine models of unilateral renovascular disease (RVD) and chronic kidney disease (CKD), which was associated with improved renal function, reduced renal inflammation, and reduced renal fibrosis. Also, ELP-VEGF targeted the kidney when administered systemically and induced similar beneficial effects on renal function and renal vascular density. The therapeutic dose of ELP-VEGF in the swine models was 0.1 mg/kg when administered intra-renally and 1.0 mg/kg when administered intravenously. The aims of the present study were to determine the maximum tolerated dose of ELP-VEGF and assess its dose-related toxicity. We hypothesize that ELP-VEGF will not exhibit toxicity at therapeutic doses. Method A dose escalating toxicology experiment was performed in Sprague Dawley. Female rats were instrumented with either carotid catheters or carotid artery telemeters for blood pressure monitoring. After a recovery period, a baseline 24-hour urine sample was collected, and baseline glomerular filtration rate (GFR) was measured by monitoring FITC-sinistrin clearance via transdermal fluorescence. A single injection of saline control or ELP-VEGF (0.1, 1, 10, 100, or 200 mg/kg) was administered, and blood pressure was monitored by telemetry or by direct carotid arterial pressure measurements. Body weights were monitored daily throughout the study, and 24-hour urine collections and GFR measurements were repeated 7 and 14 days after protein injection. On day 14 after injection, blood was collected, one kidney was collected and fixed for histological examination, and the second kidney was perfused with Microfil vascular contrast agent for quantification of renal vascular density by micro-CT. Results ELP-VEGF caused no significant changes in body weight at any dose. At the highest doses there was an acute drop in blood pressure (20 – 30 mm Hg at 100 and 200 mg/kg dose, respectively) for approximately twenty minutes post-injection which then normalized. GFR was unchanged by ELP-VEGF at doses up to 100 mg/kg. However, GFR was significantly increased 14 days after treatment with 200 mg/kg ELP-VEGF (1.5 +/- 0.3 versus 2.7 +/- 0.3 mL/min/100 g body weight, p=0.0021). Plasma toxicology revealed no changes in markers of liver or kidney toxicity (AST, ALT, BUN, creatinine, LDH, bilirubin) at any dose or time point. Renal vascular density was unaffected by ELP-VEGF at doses up to 10 mg/kg. However, at 200 mg/kg ELP-VEGF, renal vascular density was significantly decreased for small (0 – 100 micron, p=0.0007) and intermediate (100 – 200 micron, p=0.028) sized vessels Conclusion ELP-VEGF has a proven therapeutic potential for treatment of RVD and CKD at therapeutic doses ranging from 0.1 – 1.0 mg/kg in swine models. Dose escalating toxicity assessment in rats found no effect of ELP-VEGF on body weight, blood pressure, plasma markers of liver and renal toxicity, GFR, or renal vascular density at these therapeutic doses. ELP-VEGF doses of 100 – 200 mg/kg caused transient hypotension immediately after the injection and were associated with increased GFR and loss of renal vascular density, possibly indicating renal damage at ultra-high doses. We conclude that the therapeutic window for ELP-VEGF is 100 – 1,000 times the effective therapeutic dose.

scholarly journals Protective Effects of At1-Receptor Blocker and Ca Antagonist Combination on Renal Function in Salt Loaded Spontaneously Hypertensive Rats/ Протективни Ефекти На Комбинацијата На Ат1 Рецепторен Блокатор И Калциум Антагонист Врз Реналната Функција Кај Спонтано Хипертензивни Стаорци Оптоварени Со Сол

PRILOZI ◽  
2015 ◽  
Vol 36 (1) ◽  
pp. 85-91
Author(s):  
Kalina Gjorgjievska ◽  
Dimce Zafirov ◽  
Maja Jurhar-Pavlova ◽  
Svetlana Cekovska ◽  
Emilija Atanasovska ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Body Weight ◽  
Combined Treatment ◽  
Receptor Blocker ◽  
Control Group ◽  
Shr Rats ◽  
Dietary Salt ◽  
Salt Loading ◽  
Ad Libitum

Abstract Salt sensitive hypertension is known to be a contributing factor for the progression of kidney disease. This study was undertaken to investigate the role of excessive dietary salt on renal function and to evaluate the effect of valsartan and amlodipin given as a combination therapy on blood pressure and parameters specific to the renal function in salt loaded SHR rats. 48 male SHR rats at age of 20 weeks and body weight ranging between 270-350 g were used. SHR rats were divided into 3 groups: control group of rats -SHRC (n = 16) given tab water ad libitum and two salt treated groups in which tab water was replaced with a solution of NaCl (1%) from age of 8 weeks given ad libitum: SHRVAL+AMLO group (n = 16) where investigated drugs were administered at a dose of 10 mg/kg/ b.w. (valsartan) and 5 mg/kg/ b.w. (amlodipin) by gavage and SHR NaCl group (n = 16) that received saline in the same volume and the same time intervals as the SHRVAL+AMLO group. For a period of 12 weeks we have investigated the effect of the VAL+AMLO drug combination on systolic blood pressure (SBP), body weight and renal function tests. Salt loading with 1% solution in the SHR NaCl group has lead to significant increase of blood pressure, proteinuria and decrease in creatinine clearance. Combined treatment with АТ1-receptor blocker and calcium antagonist has managed to control blood pressure and ameliorated renal damage.

Angiotensin II inhibition on blood pressure and renal hemodynamics in pregnant rats

1986 ◽  
Vol 250 (2) ◽  
pp. F308-F314 ◽  
Author(s):  
C. Baylis ◽  
R. C. Collins
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renal Plasma Flow ◽  
Renal Hemodynamics ◽  
Urine Flow ◽  
Ang Ii ◽  
Pregnant Rats ◽  
Acute Surgery ◽  
Arterial Blood ◽  
Renal Vascular

Late-pregnant (18-20 days) and virgin rats were studied under anesthesia or while awake to investigate the effect of acute angiotensin II (ANG II) inhibition (with saralasin or captopril) on mean arterial blood pressure (AP) and renal hemodynamics. ANG II inhibition had no effect on AP in either anesthetized or awake virgin rats. Saralasin produced no effect on renal hemodynamics although with captopril small increases in renal plasma flow rate (RPF) and decreases in renal vascular resistance (RVR) occurred in virgins. In anesthetized pregnant rats, ANG II inhibition evoked marked decreases in AP. In some rats receiving saralasin, AP was only mildly depressed and RVR fell, leading to increases in glomerular filtration rate and RPF. In others, saralasin produced large decreases in AP, and indices of renal function became unmeasurable because of near cessation of urine flow. All late-pregnant anesthetized rats receiving captopril showed increased RPF irrespective of the magnitude of the fall in AP. In awake pregnant rats no effect on AP was seen with ANG II inhibition. Saralasin had no effect on renal hemodynamics although with captopril a small increase in RPF was observed. These data indicate that the stress of acute surgery and anesthesia produces a dependence of AP on ANG II in the pregnant but not the virgin rat. Under normal pregnant (awake) conditions, however, ANG II inhibition has no net effect on AP.

scholarly journals Effect of long-term high-fat diet intake on peripheral insulin sensibility, blood pressure, and renal function in female rats

2016 ◽  
Vol 60 (1) ◽  
pp. 28536 ◽  
Author(s):  
Noemi A. V. Roza ◽  
Luiz F. Possignolo ◽  
Adrianne C. Palanch ◽  
José A. R. Gontijo
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
High Fat Diet ◽  
Female Rats ◽  
High Fat ◽  
Diet Intake

Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats

2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Rat Kidney ◽  
Late Pregnancy ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Renal Vasoconstriction ◽  
Dependent Inhibition

20-Hydroxyeicosatetraenoic acid (20-HETE), which promotes renal vasoconstriction, is formed in the rat kidney primarily by cytochrome P-450 (CYP) 4A isoforms (4A1, 4A2, 4A3, 4A8). Nitric oxide (NO) has been shown to bind to the heme moiety of the CYP4A2 protein and to inhibit 20-HETE synthesis in renal arterioles of male rats. However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats. Incubation of recombinant CYP4A1 and 4A3 proteins with sodium nitroprusside (SNP) shifted the absorbance at 440 nm, indicating the formation of a ferric-nitrosyl-CYP4A complex. The absorbance for CYP4A3 was about twofold higher than that of CYP4A1. Incubation of SNP or peroxynitrite (PN; 0.01–1 mM) with CYP4A recombinant membranes caused a concentration-dependent inhibition of 20-HETE synthesis, with both chemicals having a greater inhibitory effect on CYP4A3-catalyzed activity. Moreover, incubation of CYP4A1 and 4A3 proteins with PN (1 mM) resulted in nitration of tyrosine residues in both proteins. In addition, PN and SNP inhibited 20-HETE synthesis in renal microvessels from female rats by 65 and 59%, respectively. We previously showed that microvessel CYP4A1/CYP4A3 expression and 20-HETE synthesis are decreased in late pregnancy. Therefore, we investigated whether such a decrease is dependent on NO, the synthesis of which has been shown to increase in late pregnancy. Administration of NG-nitro-l-arginine methyl ester (l-NAME) to pregnant rats for 6 days ( days 15- 20 of pregnancy) caused a significant increase in systolic blood pressure, which was prevented by concurrent treatment with the CYP4A inhibitor 1-aminobenzotriazole (ABT). Urinary NO2/NO3 excretion decreased by 40 and 52% in l-NAME- and l-NAME + ABT-treated groups, respectively. Interestingly, renal microvessel 20-HETE synthesis showed a marked increase following l-NAME treatment, and this increase was diminished with coadministration of ABT. These results demonstrate that NO interacts with CYP4A proteins in a distinct manner and it interferes with renal microvessel 20-HETE synthesis, which may play an important role in the regulation of blood pressure and renal function during pregnancy.

scholarly journals The effect of chronic nitric oxide inhibition on vascular reactivity and blood pressure in pregnant rats

1999 ◽  
Vol 117 (5) ◽  
pp. 197-204 ◽  
Author(s):  
Nilton Hideto Takiuti ◽  
Maria Helena Cetelli Carvalho ◽  
Soubhi Kahhale ◽  
Dorothy Nigro ◽  
Hermes Vieira Barbeiro ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Vascular Reactivity ◽  
Unit Weight ◽  
Control Group ◽  
Pregnant Rats ◽  
Nitric Oxide Inhibition ◽  
Female Wistar Rats ◽  
Main Component ◽  
Oxide Inhibition

CONTEXT: The exact mechanism involved in changes in blood pressure and peripheral vascular resistance during pregnancy is unknown. OBJECTIVE:To evaluate the importance of endothelium-derivated relaxing factor (EDRF) and its main component, nitric oxide, in blood pressure and vascular reactivity in pregnant rats. DESIGN: Clinical trial in experimentation animals. SETTING: University laboratory of Pharmacology. SAMPLE: Female Wistar rats with normal blood pressure, weight (152 to 227 grams) and age (90 to 116 days). INTERVENTION: The rats were divided in to four groups: pregnant rats treated with L-NAME (13 rats); pregnant control rats (8 rats); virgin rats treated with L-NAME (10 rats); virgin control rats (12 rats). The vascular preparations and caudal blood pressure were obtained at the end of pregnancy, or after the administration of L-NAME in virgin rats. MAIN MEASUREMENTS: The caudal blood pressure and the vascular response to acetylcholine in pre-contracted aortic rings, both with and without endothelium, and the effect of nitric oxide inhibition, Nw-L-nitro-arginine methyl-ester (L-NAME), in pregnant and virgin rats. The L-NAME was administered in the drinking water over a 10-day period. RESULTS: The blood pressure decreased in pregnancy. Aortic rings of pregnant rats were more sensitive to acetylcholine than those of virgin rats. After L-NAME treatment, the blood pressure increased and relaxation was blocked in both groups. The fetal-placental unit weight of the L-NAME group was lower than that of the control group. CONCLUSION: Acetylcholine-induced vasorelaxation sensitivity was greater in pregnant rats and that blood pressure increased after L-NAME administration while the acetylcholine-induced vasorelaxation response was blocked.

scholarly journals Aortae of Young Rats with Metabolic Syndrome Exhibit Enhanced Vasoconstrictor Activity Than Older Rats

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
R H Ali ◽  
N M B Gamil ◽  
A M Abdelrahman ◽  
M A Ahmed ◽  
G K Megahed ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Young Adult ◽  
Fasting Blood Glucose ◽  
Age Groups ◽  
Female Rats ◽  
Control Group ◽  
Albino Rats ◽  
Functional Changes ◽  
Vasoconstrictor Response ◽  
Nitrite Content

Abstract Background Metabolic syndrome (MetS) causes pathological remodeling of the heart and adjacent vessels. The functional changes in the big vessels in different age groups had not been fully delineated. Aim of the work The present study was planned to investigate aortic vasodilator and vasoconstrictor reactivity in young, adult and old female rats with MetS. Design: The experimental study was performed on 90 female albino rats randomized into 6 groups: young, adult and old rats with MetS and their respective control groups. Methods MetS was induced by feeding rats 41% fructose -containing diet and giving fructose solution (5 g fructose in 4 ml distilled water/day) by gavage in two sessions (2 ml/session). On the 8th week, all rats were sacrificed and were subjected to determination of body weight (BW), body mass index (BMI), absolute and relative visceral fat weight (VF), fasting blood glucose (FBG), plasma insulin (PI), homeostasis model of insulin resistance (HOMA-IR) and plasma lipid profile. All rats’ aortae were subjected to study of vascular reactivity to Potassium chloride (KCL), phenylephrine (PE) and acetyl choline (A.Ch) as well as estimation of nitrite content. Results On the 8th week of the study, all MetS groups developed criteria of metabolic syndrome as evidenced by the significant increase in final BW, BMI, absolute and relative VF weights, FBG, PI and HOMA-IR compared to their control group values. Also, MetS rat groups exhibited evident dyslipidemia in the form of significant increase in plasma levels of triglycerides, total cholesterol and significant decrease in HDL-cholesterol compared to their control group values. Aortae of young and adult MetS rat groups showed significant increase in their vasoconstrictor response to KCl and PE and decrease in A.Ch/KCL% and A.Ch/PE % compared to their controls, while old MetS rat group showed significantly increased vasoconstrictor response only to KCL compared to their controls. When compared to each other, young age MetS group had significantly higher vasoconstrictor response to PE compared to old MetS group despite comparable nitrite content. Conclusion Met.S causes functional vascular changes in all age groups with unexpectedly enhanced vasoconstrictor response in the young group compared to old.

High-potassium diet attenuates salt-induced acceleration of hypertension in SHR

1991 ◽  
Vol 260 (1) ◽  
pp. R21-R26 ◽  
Author(s):  
Y. Sato ◽  
K. Ando ◽  
E. Ogata ◽  
T. Fujita
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
High Potassium ◽  
Spontaneously Hypertensive ◽  
Antihypertensive Action ◽  
High K ◽  
Wistar Kyoto ◽  
Renal Vascular

We studied the effects of K supplementation (8% KCl) for 4 wk on blood pressure (BP), Na space, and renal hemodynamics in 5-wk-old, spontaneously hypertensive rats (SHR) or age-matched Wistar-Kyoto rats (WKY) eating normal-NaCl (0.66%) or high-NaCl (8%) diet. In WKY, high-Na and/or high-K diets had no effects on BP. In SHR, Na load accelerated the development of hypertension, whereas K supplementation did not affect BP of normal-Na SHR but attenuated the increase in BP with Na load. Correspondingly, Na load in SHR significantly increased renal vascular resistance (RVR), and K supplementation attenuated the increased RVR of Na-loaded SHR. Moreover, Na space of SHR was increased compared with that of WKY, and although Na load did not affect Na space, K supplementation tended to decrease Na space in SHR. These results indicate that 9-wk-old SHR is relatively volume-expanded compared with age-matched WKY, and K supplementation could improve the lowered slope of the pressure-Na excretion relationship in SHR, resulting in maintenance of Na balance. Thus the data suggest that changes in RVR, which might be intimately related to renal function for Na excretion, contribute to both salt sensitivity of SHR and antihypertensive action of K supplementation in Na-loaded SHR.

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