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.

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.

Abnormal renal medullary response to angiotensin II in SHR is corrected by long-term enalapril treatment

2001 ◽  
Vol 280 (4) ◽  
pp. R1076-R1084 ◽  
Author(s):  
Stephen A. W. Dukacz ◽  
Ming-Guo Feng ◽  
Lu-Fang Yang ◽  
Robert M. K. W. Lee ◽  
Robert L. Kline
Keyword(s):  
Renal Medulla ◽  
Term Treatment ◽  
Ang Ii ◽  
Doppler Flowmetry ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Long Term Treatment ◽  
Renal Medullary Blood Flow ◽  
Wistar Kyoto

This study tested the hypotheses that renal medullary blood flow (MBF) in spontaneously hypertensive rats (SHR) has enhanced responsiveness to angiotensin (ANG) II and that long-term treatment with enalapril can correct this. MBF, measured by laser Doppler flowmetry in anesthetized rats, was not altered significantly by ANG II in Wistar-Kyoto (WKY) rats, but was reduced dose dependently (25% at 50 ng · kg−1 · min−1) in SHR. Infusion of N G-nitro-l-arginine methyl ester (l-NAME) into the renal medulla unmasked ANG II sensitivity in WKY rats while l-arginine given into the renal medulla abolished the responses to ANG II in SHR. In 18- to 19-wk-old SHR treated with enalapril (25 mg · kg−1 · day−1 when 4 to 14 wk old), ANG II did not alter MBF significantly, but sensitivity to ANG II was unmasked after l-NAME was infused into the renal medulla. Endothelium-dependent vasodilation (assessed with aortic rings) was significantly greater in treated SHR when compared with that in control SHR. These results indicate that MBF in SHR is sensitive to low-dose ANG II and suggest that this effect may be due to an impaired counterregulatory effect of nitric oxide. Long-term treatment with enalapril improves endothelium-dependent vascular relaxation and decreases the sensitivity of MBF to ANG II. These effects may be causally related to the persistent antihypertensive action of enalapril in SHR.

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.

Role of endogenous centrally released NO in cardiovascular adaptation to hypovolemia in WKY and SHR

1997 ◽  
Vol 272 (5) ◽  
pp. H2282-H2288 ◽  
Author(s):  
P. Paczwa ◽  
A. S. Budzikowski ◽  
E. Szczepanska-Sadowska
Keyword(s):  
Heart Rate ◽  
Spontaneously Hypertensive Rats ◽  
Hypotensive Effect ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Time Control ◽  
Artificial Cerebrospinal Fluid ◽  
In Series ◽  
Wistar Kyoto

The role of endogenous centrally released nitric oxide (NO) during hypovolemia was investigated in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Bleeding of the rats (1.3% of blood volume) was performed after intracerebroventricular (ICV) administration of: 1) artificial cerebrospinal fluid (series 1, time control, 8 WKY and 8 SHR); 2) 0.5 mg NG-nitro-L-arginine (L-NNA, 2.3 nmol), an inhibitor of NO synthesis (series 2, 8 WKY and 7 SHR); and 3) 0.5 mg L-NNA followed by 1 mg (5.8 nmol) of L-arginine (L-Arg) (6 WKY and 5 SHR). In WKY, hypotension was associated with significant bradycardia (P < 0.001), whereas in SHR slight acceleration of heart rate was observed. In series 2 hemorrhage resulted in a small but significant increase of mean arterial pressure (MAP; P < 0.05) and considerable tachycardia (P < 0.001). In SHR, L-NNA did not modify the decrease of MAP during hypovolomia, and bleeding resulted in a significant bradycardia (P < 0.001). Pretreatment with L-Arg in series 3 was able to reverse the effects of L-NNA on changes of MAP and heart rate during hypovolemia. The results indicate that the central nitroxidergic system plays a significant role in eliciting hypotension and bradycardia in normotensive WKY during hemorrhage. Function of the central nitroxidergic system is significantly altered in SHR in which NO appears to prevent hemorrhagic bradycardia and to reduce the hypotensive effect.

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.

Angiotensin II acts at AT1receptors in the nucleus of the solitary tract to attenuate the baroreceptor reflex

1998 ◽  
Vol 275 (5) ◽  
pp. R1611-R1619 ◽  
Author(s):  
Kiyoshi Matsumura ◽  
David B. Averill ◽  
Carlos M. Ferrario
Keyword(s):  
Arterial Pressure ◽  
Receptor Antagonist ◽  
Baroreceptor Reflex ◽  
Ang Ii ◽  
Solitary Tract ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Reflex Control ◽  
Wistar Kyoto ◽  
Baroreceptor Reflex Control

The object of the current study was to determine if ANG II acts at type 1 (AT1) or type 2 (AT2) receptors in the nucleus of the solitary tract (NTS) to reduce baroreceptor reflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR). Experiments were carried out in urethan-anesthetized Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Reflex changes in RSNA and HR were elicited by intravenous infusion of either phenylephrine or sodium nitroprusside before and after bilateral microinjection of CV-11974 (AT1 receptor antagonist, 10 pmol), PD-123319 (AT2 receptor antagonist, 100 pmol), or artificial cerebrospinal fluid (aCSF, 50 nl) in the NTS. Mean arterial pressure (MAP)-RSNA and MAP-HR data were fit to logistic functions to analyze the baroreceptor reflex. Baroreceptor reflex sensitivities for RSNA and HR were attenuated in SHR compared with those in WKY rats. Bilateral injection of CV-11974, PD-123319, or aCSF in the NTS of either strain had no effect on baseline arterial pressure, HR, or RSNA. However, CV-11974 injected in the NTS increased significantly ( P < 0.01) the sensitivities for baroreceptor reflex control of RSNA and HR in SHR and WKY rats. Neither PD-123319 nor aCSF altered baroreceptor reflex control of RSNA and HR in either SHR or WKY rats. These results demonstrate that endogenous ANG II acts at AT1 receptors of the NTS to attenuate the baroreceptor reflex in SHR as well as in WKY rats.

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.

Central V1 AVP receptors are involved in cardiovascular adaptation to hypovolemia in WKY but not in SHR

1996 ◽  
Vol 271 (3) ◽  
pp. H1057-H1064 ◽  
Author(s):  
A. S. Budzikowski ◽  
P. Paczwa ◽  
E. Szczepanska-Sadowska
Keyword(s):  
Cardiovascular Responses ◽  
Receptor Antagonists ◽  
Question Mark ◽  
Spontaneously Hypertensive ◽  
Arterial Bleeding ◽  
Artificial Cerebrospinal Fluid ◽  
Before And After ◽  
Wistar Kyoto ◽  
Lateral Cerebral Ventricle

The present study was designed to determine the role of centrally released arginine vasopressin (AVP) in cardiovascular adaptation to hypotensive hypovolemia in conscious normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Three groups of experiments were performed on WKY and SHR chronically implanted with lateral cerebral ventricle (LCV) cannulas and with femoral artery catheters. Mean arterial pressure (MAP) and heart rate (HR) were monitored before and after arterial bleeding (1.3% body weight) performed during LCV infusion 1) artificial cerebrospinal fluid (control), 2) V1 AVP-receptor antagonists inverted question mark[d(Et2)Tyr(Me)]DAVP, 5 ng/min inverted question mark, and 3) V2 AVP-receptor antagonists inverted question mark[d(CH2)5-D-Ile2, Ile4, AlaNH2]AVP, 5 ng/min inverted question mark. In control experiments hemorrhage caused similar significant decreases of MAP in both strains and bradycardia in WKY. Blockade of central V1 AVP receptors abolished hemorrhagic bradycardia and significantly reduced hypotension in WKY, with no effect on HR and MAP responses to hypovolemia in SHR. Neither in WKY nor in SHR were the cardiovascular responses to hemorrhage altered by blockade of central V2 receptors. The results suggest that the central V1 AVP system plays a significant role in eliciting hypovolemic bradycardia and hypotension in WKY and that this function is significantly impaired in SHR.

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.

scholarly journals The effects of angiotensin-(1–7) on the exchanger NHE3 and on [Ca2+]i in the proximal tubules of spontaneously hypertensive rats

2017 ◽  
Vol 313 (2) ◽  
pp. F450-F460 ◽  
Author(s):  
Regiane Cardoso Castelo-Branco ◽  
Deise C. A. Leite-Dellova ◽  
Fernanda Barrinha Fernandes ◽  
Gerhard Malnic ◽  
Margarida de Mello-Aires
Keyword(s):  
Plasma Level ◽  
Spontaneously Hypertensive Rats ◽  
High Plasma ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
High Plasma Level ◽  
Wistar Kyoto

The acute effects of angiotensin-1–7 [ANG-(1–7)] on the reabsorptive bicarbonate flow (J[Formula: see text]) were evaluated using stationary microperfusion in vivo in the proximal tubules of spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto (WKY) rats, using a microelectrode sensitive to H+. In WKY rats, the control J[Formula: see text] was 2.40 ± 0.10 nmol·cm−2·s−1 ( n = 120); losartan (10−7 M) or A779 (10−6 M, a specific Mas antagonist), alone or in combination with losartan, decreased the J[Formula: see text]. ANG-(1–7) had biphasic effects on J[Formula: see text]: at 10−9 M, it inhibited, and at 10−6, it stimulated the flow. S3226 [10−6 M, a specific Na+-H+ exchanger 3 (NHE3) antagonist] decreased J[Formula: see text] and changed the stimulatory effect of ANG-(1–7) to an inhibitory one but did not alter the inhibitory action of ANG-(1–7). In SHR, the control J[Formula: see text] was 2.04 ± 0.13 nmol·cm−2·s−1 ( n = 56), and A779 and/or losartan reduced the flow. ANG-(1–7) at 10−9 M increased J[Formula: see text], and ANG-(1–7) at 10−6 M reduced it. The effects of A779, losartan, and S3226 on the J[Formula: see text] were similar to those found in WKY rats, which indicated that in SHR, the ANG-(1–7) action on the NHE3 was via Mas and ANG II type 1. The cytosolic calcium in the WKY or SHR rats was ~100 nM and was increased by ANG-(1–7) at 10−9 or 10−6 M. In hypertensive animals, a high plasma level of ANG-(1–7) inhibited NHE3 in the proximal tubule, which mitigated the hypertension caused by the high plasma level of ANG II.

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