The Role of Corticosteroids in the Regulation of Myocardial Na, K-ATPase in Normotensive and Spontaneously Hypertensive Rats

1984 ◽  
Vol 66 (4) ◽  
pp. 421-426 ◽  
Author(s):  
Naftali Stern ◽  
Frances W. J. Beck ◽  
Donald Walt Chandler ◽  
Douglas M. Mayes ◽  
James R. Sowers
Keyword(s):  
Atpase Activity ◽  
Glucocorticoid Receptors ◽  
Renal Tubule ◽  
Protein Therapy ◽  
Sodium Potassium ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wistar Kyoto ◽  
Adrenalectomized Rats

1. Sodium, potassium-dependent adenosine triphosphatase (ATPase) of the renal tubule is known to be dependent on both gluco- and mineralo-corticoids. Recent evidence suggests that corticosteroids may modulate ATPase activity at extrarenal sites. The myocardium contains glucocorticoid receptors to which mineralocorticoids can also bind. Thus, the possibility that myocardial ATPase is corticosteroid dependent was examined in the Wistar-Kyoto (WKY) normotensive rat and also in the spontaneously hypertensive (SH) rat, a strain previously shown to exhibit reduced myocardial ATPase activity. 2. WKY and SH rats (in groups of 10) were either sham operated or adrenalectomized and placed on 1% NaCl solution as drinking water. Adrenalectomized rats subsequently received daily intraperitoneal injections of either vehicle (1% NaCl, 0.5 ml), aldosterone (30 μg/kg) or dexamethasone (60 μg/kg). Renal cortical and myocardial ATPase activities were determined 21 days later in all groups. 3. Adrenalectomized WKY rats had reduced myocardial ATPase activity (5.15 ± 0.88 vs 8.18 ± 0.93 μmol of phosphate h−1 mg−1 of protein in controls; P < 0.01). This observed decrease in ATPase in adrenalectomized rats could be at least partly prevented by selective aldosterone or dexamethasone replacement. Parallel changes were observed with renal cortical ATPase. 4. SH rat myocardial ATPase was lower than in WKY rats (P<0.05, 5.88 ± 0.99 μmol of phosphate h−1 mg−1 of protein) and was unaffected by adrenalectomy (5.47 ± 0.68 μmol of phosphate h−1 mg−1 of protein) whether accompanied by aldosterone (6.08 ± 0.68 μmol of phosphate h−1 mg−1 of protein) or dexamethasone (6.47 ± 0.84 μmol of phosphate h−1 mg−1 of protein) therapy or not. Renal cortical ATPase, however, exhibited corticosteroid dependency in the SH rats that resembled the pattern observed in WKY rats. 5. It is suggested that the lower ATPase activity observed in SH rats after the evolution of hypertension may result from decreased sensitivity to endogenous corticosteroids.

Effect of sodium chloride and sodium bicarbonate on blood pressure in stroke-prone spontaneously hypertensive rats

1988 ◽  
Vol 74 (6) ◽  
pp. 577-585 ◽  
Author(s):  
F. C. Luft ◽  
H. Steinberg ◽  
U. Ganten ◽  
D. Meyer ◽  
K. H. Gless ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mineral Water ◽  
Sodium Reabsorption ◽  
Sodium Potassium ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Ph Values ◽  
Wistar Kyoto ◽  
Renal Sodium Reabsorption

1. To test the hypothesis that NaCl increases blood pressure, while NaHCO3 does not, we measured the effect of an NaHCO3-containing mineral water on blood pressure in stroke-prone spontaneously hypertensive (SHR-SP) and Wistar–Kyoto (WKY) rats. We compared mineral water with equimolar amounts of NaCl and demineralized drinking water in six groups of 20 rats each over 24 weeks. 2. NaCl consistently increased blood pressure in both SHR-SP and WKY compared with demineralized water, while mineral water did not. 3. We studied the possible role of sodium-regulating hormones. Sodium, potassium-dependent adenosine triphosphatase activity was decreased by NaCl and by age, but not by mineral water. The concentration of atrial natriuretic peptide was greater in SHR-SP, but was not influenced by the two regimens. Components of the renin–angiotensin–aldosterone system and 18-hydroxy-deoxycorticosterone tended to decrease with NaCl, but not with mineral water. 4. Plasma pH values in the six groups of rats were not different; however, SHR-SP had consistently lower Pco2 and HCO−3 values and higher anion gap values than WKY rats. These values were not influence by the two regimens. 5. NaCl elevates blood pressure in SHR-SP while NaHCO3 does not. The changes in hormones regulating sodium homoeostasis suggest that NaCl induces volume expansion while NaHCO3 does not. The effect may be related to influences on renal sodium reabsorption by chloride and bicarbonate. The possible role of increased proton excretory activity in SHR-SP remains to be determined.

scholarly journals Role of cholinergic receptors in adrenal catecholamine secretion in spontaneously hypertensive rats

1999 ◽  
Vol 277 (4) ◽  
pp. R1057-R1062 ◽  
Author(s):  
Takahiro Nagayama ◽  
Takayuki Matsumoto ◽  
Makoto Yoshida ◽  
Mizue Suzuki-Kusaba ◽  
Hiroaki Hisa ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Muscarinic Receptors ◽  
Nicotinic Receptors ◽  
Spontaneously Hypertensive Rats ◽  
Adrenal Glands ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wistar Kyoto

We investigated the role of nicotinic and muscarinic receptors in secretion of catecholamines induced by transmural electrical stimulation (ES) from isolated perfused adrenal glands of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. ES (1–10 Hz) produced frequency-dependent increases in epinephrine (Epi) and norepinephrine (NE) output as measured in perfusate. The ES-induced increases in NE output, but not Epi output, were significantly greater in adrenal glands of SHRs than in those of WKY rats. Hexamethonium (10–100 μM) markedly inhibited the ES-induced increases in Epi and NE output from adrenal glands of SHRs and WKY rats. Atropine (0.3–3 μM) inhibited the ES-induced increases in Epi and NE output from adrenal glands of SHRs, but not from those of WKY rats. These results suggest that endogenous acetylcholine-induced secretion of adrenal catecholamines is predominantly mediated by nicotinic receptors in SHRs and WKY rats and that the contribution of muscarinic receptors may be different between these two strains.

Role of renal nerves in onset and maintenance of spontaneous hypertension

1982 ◽  
Vol 243 (2) ◽  
pp. H284-H288 ◽  
Author(s):  
R. A. Norman ◽  
D. J. Dzielak
Keyword(s):  
Arterial Pressure ◽  
Renal Denervation ◽  
Indirect Measurement ◽  
Renal Nerves ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Norepinephrine Content ◽  
Wistar Kyoto

Renal denervation has been reported to delay development of hypertension in Okamoto spontaneously hypertensive rats (SHR) but to have no effect on the final hypertensive state. However, functional reinnervation begins to occur about 1 mo after renal denervation. The arterial pressure of SHR undergoing repeated bilateral renal denervations at the age of 4, 7, 10, 13, and 16 wk was compared with that in sham-operated SHR. In addition, the effect of successive renal denervations at 4, 7, and 10 wk of age in Wistar-Kyoto (WKY) control rats was determined. Both indirect measurement of pressure by the tail-cuff technique and mean arterial pressure (MAP) measurement indicated that renal denervation prevents full expression of hypertension in SHR. MAP in 19-wk-old renal-denervation SHR averaged 159 +/- 5.1 mmHg (SE) vs. 178 +/-0 4.2 mmHg in sham-operated SHR. Renal denervation had no effect on arterial pressure of WKY rats. Renal norepinephrine content in the renal-denervated WKY rats and SHR was less than 20% of that in the sham-operated groups. Successive bilateral renal denervations every 3 wk blocks 30-40% of the expected progressive elevation of arterial pressure in aging SHR.

scholarly journals Differential Mechanisms of Ang (1-7)-Mediated Vasodepressor Effect in Adult and Aged Candesartan-Treated Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
S. Bosnyak ◽  
R. E. Widdop ◽  
K. M. Denton ◽  
E. S. Jones
Keyword(s):  
Blood Pressure ◽  
Angiotensin Receptor ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Receptor Localization ◽  
Wistar Kyoto ◽  
Depressor Effect ◽  
Stimulation Of

Angiotensin (1-7) (Ang (1-7)) causes vasodilator effects in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) via angiotensin type 2 receptors (AT2R). However, the role of vascular AT2R in aging is not known. Therefore, we examined the effect of aging on Ang (1-7)-mediated vasodepressor effects and vascular angiotensin receptor localization in aging. Blood pressure was measured in conscious adult (~17 weeks) and aged (~19 months) normotensive rats that received drug combinations in a randomised fashion over a 4-day protocol: (i) Ang (1-7) alone, (ii) AT1R antagonist, candesartan, alone, (iii) Ang (1-7) and candesartan, or (iv) Ang-(1-7), candesartan, and the AT2R antagonist, PD123319. In a separate group of animals, the specificMasR antagonist, A779, was administered in place of PD123319. Receptor localisation was also assessed in aortic sections from adult and aged WKY rats by immunofluorescence. Ang (1-7) reduced blood pressure (~15 mmHg) in adult normotensive rats although this effect was dependant on the background dose of candesartan. This depressor effect was reversed by AT2R blockade. In aged rats, the depressor effect of Ang (1-7) was evident but was now inhibited by either AT2R blockade orMasR blockade. At the same time, AT2R,MasR, and ACE2 immunoreactivity was markedly elevated in aortic sections from aged animals. These results indicate that the Ang (1-7)-mediated depressor effect was preserved in aged animals. Whereas Ang (1-7) effects were mediated exclusively via stimulation of AT2R in adult WKY, with aging the vasodepressor effect of Ang (1-7) involved both AT2R andMasR.

Central ANG II-receptor antagonists impair cardiovascular and vasopressin response to hemorrhage in rats

1995 ◽  
Vol 268 (6) ◽  
pp. R1500-R1506 ◽  
Author(s):  
W. J. Lee ◽  
E. K. Yang ◽  
D. K. Ahn ◽  
Y. Y. Park ◽  
J. S. Park ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Physiological Role ◽  
Ang Ii ◽  
Vasopressin Release ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Artificial Cerebrospinal Fluid ◽  
Wistar Kyoto ◽  
Different Strains

The role of brain angiotensin II (ANG II) in mediating cardiovascular, vasopressin, and renin responses to hemorrhage was assessed in conscious spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto (WKY) and Wistar rats. Intracerebroventricular administration of losartan (10 micrograms) and saralasin (1 microgram.microliter-1.min-1) produced a markedly greater fall in blood pressure and a reduced tachycardia during and after hemorrhage (15 ml/kg) compared with the artificial cerebrospinal fluid control in SHR and Wistar rats but not in WKY rats. Vasopressin release after hemorrhage was also impaired, but renin release was enhanced by intracerebroventricular ANG II antagonists in SHR and Wistar rats but not in WKY rats. Losartan and saralasin produced remarkably similar effects on the cardiovascular, vasopressin, and renin responses to hemorrhage. These data suggest that brain ANG II acting through AT1 receptors plays an important physiological role in mediating rapid cardiovascular regulation and vasopressin release in response to hemorrhage. The relative importance of brain angiotensin system may vary in different strains of rate.

Na-K-ATPase in nephron segments of rats developing spontaneous hypertension

1985 ◽  
Vol 249 (6) ◽  
pp. F863-F869 ◽  
Author(s):  
L. C. Garg ◽  
N. Narang ◽  
S. McArdle
Keyword(s):  
Enzyme Activity ◽  
Atpase Activity ◽  
Collecting Duct ◽  
Thick Ascending Limb ◽  
Spontaneously Hypertensive ◽  
Nephron Segments ◽  
Medullary Thick Ascending Limb ◽  
Abnormal Pattern ◽  
Wistar Kyoto

Na-K-ATPase activity was determined in seven specific nephron segments of 5- and 12-wk-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) controls. The enzyme activity in proximal convoluted tubule (PCT) and proximal straight tubule (PST) was significantly higher in 5-wk-old SHR than in WKY. However, Na-K-ATPase activity in medullary thick ascending limb (MTAL), cortical thick ascending limb (CTAL), and distal convoluted tubule (DCT) was significantly lower in 5-wk-old SHR than in WKY. There were no significant differences in the enzyme activity in PCT, PST, MTAL, CTAL, and DCT in 12-wk-old SHR and WKY. Furthermore, there were no significant differences in Na-K-ATPase activity in collecting duct segments of 5- or 12-wk-old SHR and age-matched WKY. The possible role of the abnormal pattern of Na-K-ATPase activity in PCT, PST, MTAL, CTAL, and DCT in 5-wk-old SHR in generation of hypertension in this strain remains to be determined.

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.

Increased Pressor Responsiveness to Enkephalin in Spontaneously Hypertensive Rats: The Role of Vasopressin

1980 ◽  
Vol 59 (s6) ◽  
pp. 235s-237s ◽  
Author(s):  
R. W. Rockhold ◽  
J. T. Crofton ◽  
L. Share
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Pressor Response ◽  
Cardiovascular Effects ◽  
Hypertensive Rats ◽  
Methionine Enkephalin ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Wistar Kyoto

1. The cardiovascular effects of an enkephalin analogue were examined in spontaneously hypertensive and normotensive Wistar-Kyoto rats. (D-Ala2)-methionine enkephalin caused a biphasic increase in blood pressure and an increase in heart rate after intracerebroventricular injection. 2. The initial pressor response to (D-Ala2)-methionine enkephalin was greater in hypertensive than in normotensive rats. No difference was noted between groups during the secondary pressor response. Heart rate increases paralleled the secondary increase in blood pressure. 3. Naloxone pretreatment abolished the secondary increase in blood pressure and the tachycardia, but did not blunt the initial pressor response in female Wistar-Kyoto rats. 4. Plasma levels of arginine vasopressin were depressed during the plateau phase of the pressor response in hypertensive rats given intracerebroventricular (d-Ala2)-methionine enkephalin. 5. The results suggest that the cardiovascular effects of central enkephalin are not due to vasopressin, but may involve activation of the sympathetic nervous system.

Role of adenosine in noradrenergic neurotransmission in spontaneously hypertensive rats

1987 ◽  
Vol 253 (4) ◽  
pp. H909-H918 ◽  
Author(s):  
E. K. Jackson
Keyword(s):  
Plasma Levels ◽  
Spontaneously Hypertensive Rat ◽  
Base Line ◽  
Inhibitory Effects ◽  
Spontaneously Hypertensive ◽  
Vascular Responses ◽  
Rat Mesentery ◽  
Wistar Kyoto

The purpose of this study was to compare the in vivo role of adenosine as a modulator of noradrenergic neurotransmission in the spontaneously hypertensive rat (SHR) and Wistar-Kyoto control rat (WKY). In the in situ blood-perfused rat mesentery, vascular responses to periarterial (sympathetic) nerve stimulation (PNS) and to exogenous norepinephrine (NE) were enhanced in SHR compared with WKY. In both SHR and WKY, vascular responses to PNS were more sensitive to inhibition by adenosine than were responses to NE. At matched base-line vascular responses, compared with WKY, SHR were less sensitive to the inhibitory effects of adenosine on vascular responses to PNS, but SHR and WKY were equally sensitive with respect to adenosine-induced inhibition of responses to NE. Antagonism of adenosine receptors with 1,3-dipropyl-8-p-sulfophenylxanthine shifted the dose-response curve to exogenous adenosine sixfold to the right yet did not influence vascular responses to PNS or NE in either SHR or WKY. Furthermore, PNS did not alter either arterial or mesenteric venous plasma levels of adenosine in SHR or WKY, and plasma levels of adenosine in both strains were always lower than the calculated threshold level required to attenuate neurotransmission. It is concluded that in vivo 1) exogenous adenosine interferes with noradrenergic neurotransmission in both SHR and WKY; 2) SHR are less sensitive to the inhibitory effects of exogenous adenosine on noradrenergic neurotransmission than are WKY; 3) endogenous adenosine does not play a role in modulating neurotransmission in either strain under the conditions of this study; and 4) enhanced noradrenergic neurotransmission in the SHR is not due to defective modulation of neurotransmission by adenosine.

Hypertension in SHR rats: contribution of maternal environment

1987 ◽  
Vol 253 (4) ◽  
pp. H980-H984 ◽  
Author(s):  
M. A. Cierpial ◽  
R. McCarty
Keyword(s):  
Shr Rats ◽  
Maternal Environment ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Rearing Conditions ◽  
Blood Pressures ◽  
Wistar Kyoto ◽  
Male Subjects ◽  
Cross Fostering

The role of the maternal environment in the development of hypertension in spontaneously hypertensive (SHR) rats was evaluated using the technique of reciprocal cross fostering. Litters of SHR and Wistar-Kyoto (WKY) normotensive pups were either reared by their natural mothers, in fostered to mothers of the same strain, or cross fostered to mothers of the opposite strain shortly after birth. Litters were weaned at 21 days of age, at which time all pups were weighed. At 18-20 wk of age, resting mean arterial blood pressures (MAP) and heart rates were determined for male subjects from the six groups (2 strains X 3 rearing conditions) via an indwelling tail artery catheter. At weaning, SHR animals weighed less than WKY animals. SHRs fostered to WKY mothers were significantly heavier than control SHRs, and WKYs fostered to SHR mothers were significantly lighter than WKY controls at weaning. These body weight differences were also evident in adulthood. Cross fostering SHR pups to normotensive WKY mothers resulted in a dramatic reduction in resting MAP measured in adulthood. Conversely, cross fostering WKY pups to SHR mothers had no measurable effect on adult resting MAP. We propose that an interaction between characteristics of the SHR maternal environment and a genetic susceptibility in SHR pups is essential in triggering the full expression of the hypertensive phenotype in this animal model of human essential hypertension.

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