Role of sodium and water excretion in the antihypertensive effect of vasopressin in the spontaneously hypertensive rat

1992 ◽  
Vol 70 (10) ◽  
pp. 1309-1314 ◽  
Author(s):  
E. K. Y. Chiu ◽  
H. Wang ◽  
J. R. McNeill
Keyword(s):  
Arterial Pressure ◽  
Sodium Excretion ◽  
Spontaneously Hypertensive Rat ◽  
Control Level ◽  
Sprague Dawley ◽  
Water Excretion ◽  
Spontaneously Hypertensive ◽  
Vasopressin Infusion ◽  
Hypertensive Rat ◽  
Wistar Kyoto

Mean arterial pressure (mmHg (1 mmHg = 133.322 Pa)), sodium excretion rate (μmol∙kg−1∙min−1), and urine flow (μL∙kg−1∙min−1) were measured in conscious unrestrained spontaneously hyptertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY) before, during, and after a 3-h intravenous infusion of arginine vasopressin (20 ng∙kg−1∙min−1), an equipressor dose of phenylephrine, or an infusion of the vehicle. Cessation of the phenylephrine infusion was associated with a return of arterial pressure to preinfusion control values in both SHR and WKY. Cessation of the vasopressin infusion was also associated with a return of arterial pressure to preinfusion values in WKY. In contrast, in the SHR, arterial pressure fell from a preinfusion control level of 164 ± 6.2 to 137 ± 4 mmHg within 1 h of stopping the vasopressin infusion. Five hours after stopping the infusion, pressure was 134 ± 3 mmHg (29 ± 5 mmHg below preinfusion levels). Similar to the WKY, cessation of a vasopressin infusion was associated with a return of arterial pressure to preinfusion values in Sprague–Dawley rats. Thus, the failure to observe a hypotensive response in normotensive rats was not a peculiarity of the WKY strain. Sodium excretion rates increased during the infusions of vasopressin to a greater extent in SHR than in WKY. However, the natriuresis induced by phenylephrine was not significantly different from that generated by vasopressin in SHR, and in WKY, the natriuresis was greater for phenylephrine than for vasopressin. Urine output increased to a greater extent during the infusions of phenylephrine in both SHR and WKY than during vasopressin infusion. Because the infusions of phenylephrine were associated with either a similar or greater natriuresis and diuresis than the infusions of vasopressin, it is unlikely that the large fall in arterial pressure that occurred following the withdrawal of the vasopressin infusion (the "withdrawal-induced antihypertensive phenomenon") was related to the preceding natriuresis and diuresis.Key words: vasopressin, spontaneously hypertensive rat, sodium excretion, water excretion, renal function, phenylephrine.

Acute renal denervation produces a diuresis and natriuresis in young SHR but not WKY rats

1986 ◽  
Vol 251 (4) ◽  
pp. F655-F661 ◽  
Author(s):  
M. A. Rudd ◽  
R. S. Grippo ◽  
W. J. Arendshorst
Keyword(s):  
Sodium Excretion ◽  
Renal Denervation ◽  
Strain Differences ◽  
Urine Flow ◽  
Sprague Dawley ◽  
Renal Vasculature ◽  
Renal Nerve ◽  
Water Excretion ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Clearance experiments were conducted to determine the effect of acute unilateral renal denervation (DNX) on renal hemodynamics and salt and water excretion in anesthetized 6-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto genetic control rats (WKY). Before DNX, SHR had higher mean arterial pressure (33%) and renal vascular resistance (RVR) (57%) and lower glomerular filtration rate (GFR) (10%); urine flow and sodium excretion were similar. Following DNX in SHR, sodium and water excretion increased by 138 and 62%, respectively (P less than 0.001); GFR and RVR were unchanged. In contrast, DNX in WKY did not affect urine flow (0%) or sodium excretion (-21%). These strain differences were observed in Okamoto-Aoki rats from two sources. Effective DNX was indicated by 95% reduction of norepinephrine content 3 days after DNX in both strains. Six-week-old Sprague-Dawley and Munich-Wistar rats, in contrast to WKY, responded to DNX with a natriuresis (+182%) and diuresis (+95%) (P less than 0.001). Renal function was unaffected by sham DNX in SHR. Our results indicate that efferent renal nerve activity has little tonic influence on the renal vasculature in these young rats. Augmented neurotransmitter release and/or tubular responsiveness may be involved in fluid and electrolyte retention and the pathogenesis of hypertension in SHR. Conversely, blunted renal neuroeffector responses may prevent WKY from developing hypertension.

Renal hemodynamics and sodium excretion in stroke-prone spontaneously hypertensive rats

1981 ◽  
Vol 241 (3) ◽  
pp. F244-F249 ◽  
Author(s):  
A. Nagaoka ◽  
M. Kakihana ◽  
M. Suno ◽  
K. Hamajo
Keyword(s):  
Arterial Pressure ◽  
Sodium Excretion ◽  
Spontaneously Hypertensive Rats ◽  
Renal Perfusion ◽  
Renal Hemodynamics ◽  
Hypertensive Rats ◽  
Water Excretion ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Renal Vascular

Renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), and sodium and water excretion were measured in anesthetized stroke-prone spontaneously hypertensive rats (SHRSP), spontaneously hypertensive rats (SHR), and control Wistar-Kyoto rats (WKY) at 9 wk of age. Mean arterial pressure in SHRSP and SHR was significantly higher than that in WKY. RBF was slightly increased in SHR and decreased in SHRSP. RVR was markedly elevated only in SHRSP. In both strains of SHR, GFR was significantly increased but water and sodium excretion were similar. When renal perfusion pressure in both strains of SHR was reduced to a level similar to that of WKY by aortic constriction, RBF was slightly but significantly reduced in both SHRSP and SHR, and GFR only in SHRSP. RVR in SHRSP was still higher. Sodium and water excretion were markedly decreased in both SHR and SHRSP. The data suggest that SHRSP are characterized by an alteration in renal hemodynamics at a young age and support the hypothesis that kidneys of SHR require a higher arterial pressure than kidneys of WKY to excrete a given amount of salt and water.

Enhanced renal sensitivity of the spontaneously hypertensive rat to urotensin II

2008 ◽  
Vol 295 (4) ◽  
pp. F1239-F1247 ◽  
Author(s):  
Alaa E. S. Abdel-Razik ◽  
Richard J. Balment ◽  
Nick Ashton
Keyword(s):  
Renal Function ◽  
Spontaneously Hypertensive Rat ◽  
Renal Medulla ◽  
Fractional Excretion ◽  
Urotensin Ii ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Hypertensive Rat ◽  
Fractional Excretion Of Sodium ◽  
Wistar Kyoto

Urotensin II (UII) has been implicated widely in cardiovascular disease. The mechanism(s) through which it contributes to elevated blood pressure is unknown, but its emerging role as a regulator of mammalian renal function suggests that the kidney might be involved. The aim of this study was to determine the effect of UII on renal function in the spontaneously hypertensive rat (SHR). UII infusion (6 pmol·min−1·100 g body wt−1) in anesthetized SHR and control Wistar-Kyoto (WKY) rats produced marked reductions in glomerular filtration rate (ΔGFR WKY, n = 7, −0.3 ± 0.1 vs. SHR, n = 7, −0.6 ± 0.1 ml·min−1·100 g body wt−1, P = 0.03), urine flow, and sodium excretion rates, which were greater in SHR by comparison with WKY rats. WKY rats also showed an increase in fractional excretion of sodium (ΔFENa; +0.6 ± 0.1%, P = 0.02) in contrast to SHR in which no such change was observed (ΔFENa −0.6 ± 0.2%). Blockade of the UII receptor (UT), and thus endogenous UII activity, with urantide evoked an increase in GFR which was greater in SHR (+0.3 ± 0.1) compared with WKY rats (+0.1 ± 0.1 ml·min−1·100 g body wt−1, P = 0.04) and was accompanied by a diuresis and natriuresis. UII and UT mRNA expression were greater in the renal medulla than the cortex of both strains; however, expression levels were up to threefold higher in SHR tissue. SHR are more sensitive than WKY to UII, which acts primarily to lower GFR thus favoring salt retention in this model of hypertension.

Hypoxic moderation of systemic hypertension in the spontaneously hypertensive rat

1987 ◽  
Vol 252 (3) ◽  
pp. R554-R561 ◽  
Author(s):  
W. N. Henley ◽  
A. Tucker
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Metabolic Adaptation ◽  
Systemic Hypertension ◽  
Thyroid Status ◽  
Blood Pressure Elevation ◽  
Spontaneously Hypertensive ◽  
Moderate Hypobaric Hypoxia ◽  
Hypertensive Rat ◽  
Wistar Kyoto

The mechanism by which chronic, moderate, hypobaric hypoxia attenuates systemic systolic blood pressure (SBP) in the spontaneously hypertensive rat (SHR) was investigated in a three-part study. In experiment 1, 10 wk of hypoxia (3,658 m altitude) commencing in 7-wk-old rats was partially effective in preventing the rise in SBP [hypoxic SHR (SHR-H) 154 mmHg vs. normoxic SHR (SHR-N) 180 mmHg; P less than 0.01]. When hypoxia was initiated in 5-wk-old SHR (experiments 2 and 3), protection against hypertension was nearly complete (experiment 2: SHR-H 122 mmHg vs. SHR-N 175 mmHg; P less than 0.001; experiment 3: 135 vs. 152 mmHg, respectively; P less than 0.05). Elevations in O2 consumption (VO2) and rectal temperature (Tre) in SHR vs. normotensive [Wistar-Kyoto (WKY)] rats provided evidence that the SHR is a hypermetabolic animal. Thyroid hormonal indices suggested that SHR changed from a low to high thyroid status at a time that rapid blood pressure elevation occurred; however, hypoxia did not influence thyroid status. Acute, significant decrements in VO2 and Tre in SHR-H (experiments 2 and 3) accompanied the attenuation of SBP by hypoxia, whereas large decrements in VO2 and SBP did not occur in hypoxic WKY. Timely administration of moderate hypoxia protects against the development of hypertension in the SHR. This protection may relate to a metabolic adaptation made by the hypoxic SHR.

High-NaCl diets increase natriuretic and diuretic responses in salt-resistant but not salt-sensitive SHR

1991 ◽  
Vol 260 (6) ◽  
pp. F890-F897 ◽  
Author(s):  
M. S. Mozaffari ◽  
S. Jirakulsomchok ◽  
Z. H. Shao ◽  
J. M. Wyss
Keyword(s):  
Arterial Pressure ◽  
Renal Denervation ◽  
Isotonic Saline ◽  
Renal Nerves ◽  
Sprague Dawley ◽  
Volume Loading ◽  
Spontaneously Hypertensive ◽  
Volume Load ◽  
Sprague Dawley Rats ◽  
Wistar Kyoto

This study tested the hypothesis that NaCl-sensitive spontaneously hypertensive rats (SHR-S) display a defect in natriuretic and diuretic responses to acute volume loading that contributes to the rise in arterial pressure observed when the rats are fed a high-NaCl diet. Seven-week-old SHR-S and NaCl-resistant SHR rats (SHR-R) and normotensive (Wistar-Kyoto and Sprague-Dawley rats) were fed high- or basal NaCl diets. After 2.5 wk on the diets, preinstrumented conscious rats received an intravenous infusion (5% body wt; 0.5 ml/min) of isotonic saline, and urine was collected through a bladder catheter for 90 min. Control rats on the high-NaCl diet (compared with basal) excreted a significantly greater percentage of Na+ and volume load. In contrast, SHR-S on high-NaCl diet (compared with basal) had a very small increase in natriuretic response and no increase in diuretic response to volume expansion. The effect of renal denervation on natriuretic and diuretic responses to volume load was tested. In SHR-R on 1 and 8% NaCl diets, renal denervation had little or no effect on these responses, suggesting that renal nerves do not play a prominent role in the dietary NaCl-induced increases in the natriuretic and diuretic responses to volume load. These results demonstrate that NaCl-resistant rats rapidly adapt to diets high in NaCl content with increased natriuretic and diuretic responses to acute volume loading. The failure of SHR-S to adapt to the dietary challenge may result in volume loading and a secondary increase in arterial pressure after feeding.

Adrenaline Neurons and PNMT Activity in the Brain and Spinal Cord of Genetically Hypertensive Rats and Rats with DOCA—salt Hypertension

1981 ◽  
Vol 61 (s7) ◽  
pp. 219s-221s ◽  
Author(s):  
J. P. Chalmers ◽  
P. R. C. Howe ◽  
Y. Wallmann ◽  
I. Tumuls
Keyword(s):  
Spinal Cord ◽  
Spontaneously Hypertensive Rat ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Genetically Hypertensive Rats ◽  
Salt Hypertension ◽  
Old Rats ◽  
Wistar Kyoto ◽  
Genetically Hypertensive

1. We have studied the number of phenylethanolamine-N-methyltransferase (PNMT)-containing nerve cells in the medulla and the activity of PNMT in the medulla, spinal cord and hypothalamus of the rat. 2. At 4 weeks of age there was an increase in the number of PNMT cells counted in the medulla of the spontaneously hypertensive rat (SHR; 21%, P < 0.01) and the stroke-prone spontaneously hypertensive rat (SHR-SP; 22%, P < 0.01) compared with the Wistar-Kyoto (WKY) control rat. 3. At 4 months of age there were no significant differences in the number of medullary PNMT cells in two normotensive strains (WKY and Fisher rats), two genetically hypertensive strains (SHR and SHR-SP) and in DOCA-salt hypertensive rats. 4. In four week old rats the activity of PNMT was increased by about 50% in the spinal cord and medulla of the SHR and SHR-SP compared with the WKY rats, and immunotitration experiments suggest that this is due to an increased concentration of enzyme. 5. At 4 months of age there were no increases in PNMT activity of either genetically hypertensive rats or DOCA-salt hypertensive rats.

Hypothalamic angiotensin receptor subtypes in normotensive and hypertensive rats

1998 ◽  
Vol 275 (2) ◽  
pp. H703-H709 ◽  
Author(s):  
N. L. Han ◽  
M. K. Sim
Keyword(s):  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rat ◽  
Renin Angiotensin System ◽  
Receptor Subtypes ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Angiotensin Iii ◽  
Displacement Experiments ◽  
Wistar Kyoto Rat ◽  
Wistar Kyoto

The binding of125I-labeled [Sar1,Ile8]angiotensin II to the hypothalamic membranes of the normotensive Wistar-Kyoto rat (WKY) and the spontaneously hypertensive rat (SHR) was studied. Displacement experiments with four centrally active angiotensins, losartan, and PD-123319 confirm the known existence of angiotensin AT1 and AT2 receptors in the rat hypothalamus. The values of the inhibitory constants for angiotensin II and PD-123319 in the SHR were significantly lower than the corresponding values in the WKY, indicating the possible existence of high-affinity hypothalamic AT1 and AT2 receptors for the two ligands in the SHR. The angiotensin AT1receptor was further separated into a 5′-guanylyl imidodiphosphate-sensitive and -nonsensitive subtype, indicating that one of the subtypes is G protein coupled. The SHR has significantly higher numbers of measurable AT1-receptor subtypes as well as AT2 receptor subtypes. The former data support the findings of other investigators showing that the hypothalamus of the SHR expressed more AT1A and AT1B mRNAs than that of the normotensive rat. Des-Asp1-angiotensin I, which is known to attenuate the central pressor action of angiotensin II and angiotensin III, acts on both the AT1 and AT2 receptors, although it has a higher affinity for the AT1receptors. The overall increase in the number of AT1 and AT2 receptors in the SHR is in line with the contention that the brain of the hypertensive rat, compared with that of the WKY, has a hyperactive renin-angiotensin system.

Impaired renal D1-like and D2-like dopamine receptor interaction in the spontaneously hypertensive rat

2001 ◽  
Vol 281 (4) ◽  
pp. R1071-R1078 ◽  
Author(s):  
Cecilia A. Ladines ◽  
Chunyu Zeng ◽  
Laureano D. Asico ◽  
Xiaoguang Sun ◽  
Felice Pocchiari ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Sodium Excretion ◽  
Spontaneously Hypertensive Rat ◽  
Rank Order ◽  
Urine Flow ◽  
Receptor Interaction ◽  
Dopamine Receptor Agonist ◽  
Renal Tubules ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

D1-like (D1, D5) and D2-like (D2, D3, D4) dopamine receptors interact in the kidney to produce a natriuresis and a diuresis. Disruption of D1 or D3 receptors in mice results in hypertension that is caused, in part, by a decreased ability to excrete an acute saline load. We studied D1-like and D2-like receptor interaction in anesthetized spontaneously hypertensive rats (SHR) by the intrarenal infusion of Z-1046 (a novel dopamine receptor agonist with rank order potency of D3≥D4>D2>D5>D1). Z-1046 increased glomerular filtration rate (GFR), urine flow, and sodium excretion in normotensive Wistar-Kyoto rats but not in SHRs. The lack of responsiveness to Z-1046 in SHRs was not an epiphenomenon, because intrarenal cholecystokinin infusion increased GFR, urine flow, and sodium excretion to a similar extent in the two rat strains. We conclude that renal D1-like and D2-like receptor interaction is impaired in SHRs. The impaired D1-like and D2-like receptor interaction in SHRs is not caused by alterations in the coding sequence of the D3 receptor, the D2-like receptor expressed in rat renal tubules that has been shown to be involved in sodium transport. Because the diuretic and natriuretic effects of D1-like receptors are, in part, caused by an interaction with D2-like receptors, it is possible that the decreased Z-1046 action in SHRs is secondary to the renal D1-like receptor dysfunction in this rat strain.

scholarly journals Suppression of endoplasmic reticulum stress improves endothelium-dependent contractile responses in aorta of the spontaneously hypertensive rat

2013 ◽  
Vol 305 (3) ◽  
pp. H344-H353 ◽  
Author(s):  
Kathryn M. Spitler ◽  
Takayuki Matsumoto ◽  
R. Clinton Webb
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Spontaneously Hypertensive Rat ◽  
Peripheral Resistance ◽  
Spontaneously Hypertensive ◽  
Cytosolic Phospholipase ◽  
Hypertensive Rat ◽  
Tert Butyl Hydroperoxide ◽  
Extracellular Signal ◽  
Wistar Kyoto

A contributing factor to increased peripheral resistance seen during hypertension is an increased production of endothelium-derived contractile factors (EDCFs). The main EDCFs are vasoconstrictor prostanoids, metabolites of arachidonic acid (AA) produced by Ca2+-dependent cytosolic phospholipase A2 (cPLA2) following phosphorylation (at Ser505) mediated by extracellular signal-regulated kinase (ERK1/2) and cyclooxygenase (COX) activations. Although endoplasmic reticulum (ER) stress has been shown to contribute to pathophysiological alterations in cardiovascular diseases, the relationship between ER stress and EDCF-mediated responses remains unclear. We tested the hypothesis that ER stress plays a role in EDCF-mediated responses via activation of the cPLA2/COX pathway in the aorta of the spontaneously hypertensive rat (SHR). Male SHR and Wistar-Kyoto rats (WKY) were treated with ER stress inhibitor, tauroursodeoxycholic acid or 4-phenlybutyric acid (TUDCA or PBA, respectively, 100 mg·kg−1·day−1 ip) or PBS (control, 300 μl/day ip) for 1 wk. There was a decrease in systolic blood pressure in SHR treated with TUDCA or PBA compared with control SHR (176 ± 3 or 181 ± 5, respectively vs. 200 ± 2 mmHg). In the SHR, treatment with TUDCA or PBA normalized aortic (vs. control SHR) 1) contractions to acetylcholine (ACh), AA, and tert-butyl hydroperoxide, 2) ACh-stimulated releases of prostanoids (thromboxane A2, PGF2α, and prostacyclin), 3) expression of COX-1, 4) phosphorylation of cPLA2 and ERK1/2, and 5) production of H2O2. Our findings demonstrate a novel interplay between ER stress and EDCF-mediated responses in the aorta of the SHR. Moreover, ER stress inhibition normalizes such responses by suppressing the cPLA2/COX pathway.

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