scholarly journals Endogenous dopamine regulates phosphate reabsorption but not NaK-ATPase in spontaneously hypertensive rat kidneys.

1994 ◽  
Vol 5 (4) ◽  
pp. 1125-1132
Author(s):  
A Debska-Slizien ◽  
P Ho ◽  
R Drangova ◽  
A D Baines
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Membrane Vesicle ◽  
Proximal Tubules ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Endogenous Dopamine ◽  
Hypertensive Rat ◽  
Wistar Kyoto ◽  
Signaling Process ◽  
Rat Kidneys

Dopamine's modulatory actions on signal transduction in the spontaneously hypertensive rat (SHR) proximal tubule are blunted; therefore, it was predicted that dopamine does not regulate phosphate (Pi) reabsorption in SHR. To test this hypothesis, dopamine production was inhibited with carbidopa (10 mg/kg ip) 18 h before and during clearance measurements of chronically denervated SHR and Wistar-Kyoto (WKY) rat kidneys. Dopamine excretion decreased 80% from SHR and 85% from WKY rats. Pi excretion decreased 60 to 67%. Plasma Pi and calcium, inulin clearance, and Na excretion did not change. Citrate excretion, which reflects proton secretion by proximal tubules, decreased 72% from WKY rats. Citrate excretion was significantly lower from SHR (5 +/- 10 pmol/min) than from WKY rats (73 +/- 11 pmol/min) and was not altered by carbidopa. Carbidopa, injected 18 and 1 h before kidneys were collected, increased NaK-ATPase in cortical basolateral membranes from WKY rats (27%) but not in membranes from SHR. After the incubation of renal cortical minceates for 15 min with L-DOPA (10(-5) M), there was no change in brush border membrane vesicle uptake of 32Pi, (3H)glucose, or (14C)citrate. Incubation with carbidopa (10(-4) M) increased 32Pi uptake by 11% (P < 0.001) and (3H)glucose uptake by 9% (P = 0.02). (14C)citrate uptake was not increased by carbidopa but was higher in SHR (977 +/- 2 pmol/10 s.mg) than in WKY rats (823 +/- 43 pmol/10 s.mg; P = 0.04). In summary, dopamine produced in WKY rat and SHR proximal tubules decreases Pi uptake by using a signaling process distinct from those that regulate NaK-ATPase and the antiporter.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Blood pressure responsiveness during the development of hypertension in the conscious spontaneously hypertensive rat

1985 ◽  
Vol 63 (10) ◽  
pp. 1258-1262 ◽  
Author(s):  
Corey B. Toal ◽  
Frans H. H. Leenen
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rat ◽  
Blood Pressure Response ◽  
Receptor Occupancy ◽  
Pressure Response ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Freely Moving ◽  
Wistar Kyoto

Blood pressure responsiveness to iv noradrenaline and angiotensin II was studied in conscious, freely moving, age-matched spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 to 16 weeks of age. At 4 and 6 weeks the SHR showed small, but nonsignificant increases in responsiveness compared with WKY to both noradrenaline and angiotensin II. At 8 weeks they exhibited similar responses to the WKY. Subsequently, at 12 and 16 weeks decreased responsiveness to noradrenaline (nonsignificant) and angiotensin II (p < 0.05 at 12 and 16 weeks) was observed in SHR versus WKY. At 16 weeks of age, hexamethonium caused potentiation of the blood pressure response to noradrenaline and angiotensin II, but to the same degree in the two strains. Captopril at this age did not elicit potentiation to noradrenaline or angiotensin II in either strain. These results indicate that there is no rise in blood pressure responsiveness to circulating pressor agents, parallel to the development of hypertension in SHR. Increased receptor occupancy or more active attenuating reflexes in SHR versus WKY appear not to be involved in the absence of hyperresponsiveness in intact consious SHR at 16 weeks of age.

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 &lt; 0.01) and the stroke-prone spontaneously hypertensive rat (SHR-SP; 22%, P &lt; 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.

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.

Vasodilation mediated by human PTH 1-34 in the spontaneously hypertensive rat

1984 ◽  
Vol 246 (1) ◽  
pp. F96-F100 ◽  
Author(s):  
D. A. McCarron ◽  
D. H. Ellison ◽  
S. Anderson
Keyword(s):  
Spontaneously Hypertensive Rat ◽  
Ionized Calcium ◽  
Experimental Hypertension ◽  
Base Line ◽  
Response Curves ◽  
Hypotensive Action ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Serum Ionized Calcium ◽  
Wistar Kyoto

Parathyroid hormone's cardiovascular effects were assessed in a model of experimental hypertension with known abnormalities of calcium metabolism. Mean arterial pressure (MAP) changes and serum ionized calcium responses were measured in the spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar-Kyoto (WKY), following injections of synthetic human PTH 1-34. Six 22-wk-old SHR and six WKY were given intra-arterial serial injections (0.1-100 micrograms/kg) of hPTH 1-34. Both the SHR (P less than 0.001) and WKY (P less than 0.001) demonstrated log dose-dependent hypotensive responses that were maximal at 1 min, with recovery occurring between 15 and 30 min. The slopes, however, of the dose-response curves differed (P less than 0.01). The SHR experienced a greater maximal delta MAP [-93.7 +/- 2.4 (SHR) vs. -71.2 +/- 1.6 mmHg (WKY), P less than 0.01]. Furthermore, the duration of the hypotensive action of hPTH 1-34 was significantly longer (P less than 0.001) in the SHR. Even when corrected for base-line MAP the SHR demonstrated a significant (P = 0.025) enhancement of this vasodilator response at doses of 5 micrograms/kg and greater at time intervals between 3 and 9 min after injection. A transient decrease [2.25 +/- 0.10 (pre) vs. 2.17 +/- 0.11 meq/liter (1 min post), P less than 0.01] in serum ionized calcium occurred at 1 min. We conclude that hPTH 1-34 is a potent vasoactive peptide in both the normotensive WKY and the SHR. The greater maximal hypotensive response to hPTH 1-34 and the prolongation of this cardiovascular effect in the SHR may be an additional manifestation of this experimental animal's acknowledged abnormalities of cellular membrane calcium and phospholipid metabolism.

Sign in / Sign up

Export Citation Format

Share Document