Vasopressin V2 receptor enhances gain of baroreflex in conscious spontaneously hypertensive rats

1999 ◽  
Vol 276 (3) ◽  
pp. R872-R879 ◽  
Author(s):  
Donella B. Sampey ◽  
Louise M. Burrell ◽  
Robert E. Widdop
Keyword(s):  
Receptor Antagonist ◽  
Spontaneously Hypertensive Rats ◽  
Pressor Response ◽  
Receptor Subtype ◽  
Hypertensive Rats ◽  
Receptor Antagonists ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Baroreflex Function ◽  
Shr And Wky Rats

The aim of the present study was to determine the receptor subtype involved in arginine vasopressin (AVP)-induced modulation of baroreflex function in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats using novel nonpeptide AVP V1- and V2-receptor antagonists. Baroreceptor heart rate (HR) reflex was investigated in both SHR and WKY rats which were intravenously administered the selective V1- and V2-receptor antagonists OPC-21268 and OPC-31260, respectively. Baroreflex function was assessed by obtaining alternate pressor and depressor responses to phenylephrine and sodium nitroprusside, respectively, to construct baroreflex curves. In both SHR and WKY rats baroreflex activity was tested before and after intravenous administration of vehicle (20% DMSO), OPC-21268 (10 mg/kg), and OPC-31260 (1 and 10 mg/kg). Vehicle did not significantly alter basal mean arterial pressure (MAP) and HR values or baroreflex function in SHR or WKY rats. The V1-receptor antagonist had no significant effect on resting MAP or HR values or on baroreflex parameters in both groups of rats, although this dose was shown to significantly inhibit the pressor response to AVP (5 ng iv; ANOVA, P < 0.05). In SHR but not WKY rats the V2-receptor antagonist significantly attenuated the gain (or slope) of the baroreflex curve (to 73 ± 3 and 79 ± 7% of control for 1 and 10 mg/kg, respectively), although AVP-induced pressor responses were also attenuated with the higher dose of the V2-receptor antagonist. These findings suggest that AVP tonically enhances baroreflex function through a V2 receptor in the SHR.

Methionine-enkephalin and vasopressin in SHR: effects of dehydration

1986 ◽  
Vol 250 (6) ◽  
pp. R1007-R1013
Author(s):  
K. Ota ◽  
L. Share ◽  
J. T. Crofton ◽  
D. P. Brooks
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Posterior Pituitary ◽  
Hypertensive Rats ◽  
Methionine Enkephalin ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Plasma Vasopressin ◽  
Vasopressin Secretion ◽  
Wistar Kyoto ◽  
Shr And Wky Rats

Enkephalins are found in the posterior pituitary, can alter vasopressin secretion, and have greater pressor effects in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto (WKY) rats. Measurement of the plasma methionine-enkephalin concentration (PMet-Enk) has provided equivocal results in humans and has not been reported in rats. We have developed a highly specific and sensitive Met-Enk radioimmunoassay and determined that Met-Enk circulates in rats but that PMet-Enk is no different between SHR and WKY rats (7.6 +/- 0.8 and 9.2 +/- 0.8 pg/ml, respectively). Water deprivation for 48 h increased the plasma vasopressin concentration (PADH) and 24-h urinary vasopressin excretion (UADHV) in SHR and WKY rats, but PMet-Enk was not altered. There were no differences in PADH and UADHV between SHR and WKY rats in either the euhydrated or dehydrated state. These results suggest that it is unlikely that circulating Met-Enk contributes importantly to the maintenance of hypertension in SHR. There was also no evidence for a greater secretion of vasopressin in SHR than in WKY rats, in contrast to previous reports.

Clonidine fails to reduce pressor responsiveness of conscious spontaneously hypertensive rats to vasopressin

1986 ◽  
Vol 64 (3) ◽  
pp. 284-289 ◽  
Author(s):  
Sunil Datar ◽  
William H. Laverty ◽  
J. Robert McNeill
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Reflex Activity ◽  
Unexpected Finding ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wistar Kyoto ◽  
Shr And Wky Rats

Pressor responses and heart rate responses to intravenous injections (3.5–50.0 pmol/kg) of arginine vasopressin (AVP) were recorded in saline- and clonidine-treated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Clonidine (20 μg/kg, i. v.) caused a marked fall of arterial pressure in SHR but not in WKY rats so that, 20 min after the injection of the α2-adrenoceptor agonist, arterial pressure was similar in the two strains of rats. The curve expressing the relationship between the dose of AVP and the increase of arterial pressure for saline-treated SHR was positioned to the left of that for saline-treated WKY rats. This enhanced pressor responsiveness of SHR to AVP may have been related to impaired reflex activity since heart rate fell much less in SHR than in WKY rats for a given elevation in pressure. Pressure responses to AVP were augmented by clonidine in both SHR and WKY rats so that, similar to saline-treated rats, pressor responsiveness to the peptide was still greater in SHR. Heart rate responses to AVP were not altered significantly by clonidine. The results indicate that clonidine fails to enhance reflex activity and reduce pressor responsiveness of SHR to AVP. The increased pressor responsiveness of both SHR and WKY rats to AVP following clonidine was an unexpected finding and may be related to a peripheral interaction between α-adrenergic agonists and AVP.

Hypertension without peripheral insulin resistance in spontaneously hypertensive rats

1992 ◽  
Vol 262 (1) ◽  
pp. E14-E19 ◽  
Author(s):  
T. A. Buchanan ◽  
G. F. Sipos ◽  
N. Madrilejo ◽  
C. Liu ◽  
V. M. Campese
Keyword(s):  
Insulin Resistance ◽  
Spontaneously Hypertensive Rats ◽  
Glucose Disposal ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Peripheral Insulin Resistance ◽  
Glucose Clearance ◽  
Glucose Output ◽  
Shr And Wky Rats

We performed euglycemic clamp studies with labeled glucose to measure insulin's effect on hepatic glucose output (HGO) and peripheral glucose clearance in eight conscious mobile spontaneously hypertensive rats (SHR) and eleven normotensive Wistar-Kyoto (WKY) rats age 9-10 wk. Systolic blood pressure was elevated in the SHR (P less than 0.001), whereas means of 12-h-fasted plasma insulin (P greater than 0.4), glucose (P greater than 0.07), HGO (P greater than 0.25), and glucose clearance (P greater than 0.2) did not differ significantly between groups. Infusions of human insulin into SHR and WKY rats (1 and 1.5 mU.min-1.kg-1, respectively) during concomitant somatostatin administration reestablished basal insulinemia in both groups. Neither HGO (P greater than 0.15) nor glucose clearance (P greater than 0.3) differed significantly between SHR and WKY rats under those conditions. Somatostatin plus higher-dose insulin infusions (4 mU.min-1.kg-1 in SHR and 3 or 6 mU.min-1.kg-1 in WKY rats) resulted in physiological hyperinsulinemia in all rats. Insulin sensitivity, calculated as the increase in glucose clearance effected by an increase in circulating insulin during higher-dose insulin infusions, did not differ significantly between SHR and WKY groups (P greater than 0.3). HGO was completely suppressed in SHR and WKY rats during the higher-dose insulin infusions. Our data indicate that hypertension is present in SHR at an age when insulin-mediated glucose disposal is not different from age-matched WKY rats. These findings do not support a role for peripheral insulin resistance in the genesis of hypertension in SHR.

Effects of dietary sodium on central and peripheral ouabain-like activity in spontaneously hypertensive rats

1993 ◽  
Vol 264 (6) ◽  
pp. H2051-H2055 ◽  
Author(s):  
F. H. Leenen ◽  
E. Harmsen ◽  
H. Yu ◽  
C. Ou
Keyword(s):  
Left Ventricle ◽  
Sympathetic Activity ◽  
Spontaneously Hypertensive Rats ◽  
Dietary Sodium ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wistar Kyoto ◽  
Later Phase ◽  
Shr And Wky Rats

High dietary Na+ intake enhances pressor and sympathoexcitatory responses in spontaneously hypertensive rats (SHR) but not Wistar-Kyoto (WKY) rats. To evaluate the possible contribution of central ouabain-like activity (OLA), brain and peripheral OLA was assessed in SHR vs. WKY rats at 4 wk of age and after 2 and 4 wk of high vs. control Na+ intake started at 4 wk of age. In SHR, hypertension developed with maturation and was exacerbated by high Na+ intake. With control Na+ intake, SHR showed higher OLA at 4, 6, and 8 wk of age in the pituitary and hypothalamus and also by 8 wk in the adrenals and left ventricle but not in plasma. High Na+ intake increased OLA in all tissues examined in both WKY rats and SHR. After 2 wk on high Na+, only OLA in hypothalamus and pituitary was higher in SHR vs. WKY rats; after 4 wk on high Na+, peripheral (i.e., adrenals, left ventricle, and plasma) OLA was also higher. These results indicate that in SHR the development of hypertension is associated early on with increases in central OLA and in a later phase with increases in peripheral OLA as well. High Na+ intake increases OLA in both SHR and WKY rats, but the higher OLA may affect sympathetic activity and blood pressure only in SHR.

Ventrolateral medulla in spontaneously hypertensive rats: role of angiotensin II

1993 ◽  
Vol 264 (2) ◽  
pp. R388-R395 ◽  
Author(s):  
H. Muratani ◽  
C. M. Ferrario ◽  
D. B. Averill
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rats ◽  
Pressor Response ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Gamma Aminobutyric Acid ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats

We investigated whether angiotensin II (ANG II), endogenous to the ventrolateral medulla (VLM), contributes to cardiovascular regulation in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The action of ANG II endogenous to the VLM was examined by microinjection of 100 pmol of [Sar1,Thr8]ANG II into either the rostral (R) or caudal (C) VLM. This ANG II antagonist caused depressor and bradycardic responses in the RVLM and pressor and tachycardic responses in the CVLM. The magnitude of the blood pressure responses was significantly greater (P < 0.01 in RVLM and P < 0.05 in CVLM) in SHRs (-27 +/- 3 mmHg in RVLM and 29 +/- 4 mmHg in CVLM) than in WKY rats (-17 +/- 1 and 17 +/- 2 mmHg, respectively). Suppression of tonic activity of RVLM neurons by bilateral injection of muscimol in the RVLM showed that the pressor response produced by ANG II antagonist injection in the CVLM required the integrity of rostral pressor neurons. The present data suggest that ANG II endogenous to RVLM and CVLM acts as a tonic excitatory agent on vasomotor neurons of the VLM. The contribution of ANG II in the RVLM and CVLM to the prevailing level of blood pressure was significantly (P < 0.01) larger in SHRs vs. WKY rats when the effect of ANG II blockade was measured as the change in blood pressure. Blockade of gamma-aminobutyric acid (GABA)A receptors in the RVLM showed that inhibitory GABAergic input to the RVLM was not diminished in this strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of acute renal denervation and ANF on renal function in adult spontaneously hypertensive rats

1991 ◽  
Vol 261 (4) ◽  
pp. R835-R841
Author(s):  
D. M. Pollock ◽  
W. J. Arendshorst
Keyword(s):  
Renal Function ◽  
Spontaneously Hypertensive Rats ◽  
Renal Denervation ◽  
Renal Nerves ◽  
Hypertensive Rats ◽  
Water Excretion ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Fractional Excretion Of Sodium ◽  
Shr And Wky Rats

Experiments were designed to evaluate the influence of the renal efferent nerves on baseline renal function and on the renal response to atrial natriuretic factor (ANF) in euvolemic anesthetized 10- to 12-wk-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) and Munich-Wistar (MW) rats. Acute unilateral renal denervation produced increases in absolute and fractional excretion of sodium and water by the ipsilateral kidney that were similar in SHR and WKY rats; larger responses were observed in MW rats. Excretion by the contralateral innervated kidney was unchanged in each group. Intravenous infusion of ANF (0.25 microgram.kg-1.min-1) caused a diuresis and natriuresis that was similar in the three strains and independent of changes in glomerular filtration rate and renal blood flow. The excretory responses to ANF were larger in denervated than in innervated kidneys. The magnitude of the natriuresis and diuresis produced by ANF was directly related to the pre-ANF rate of urinary excretion, suggesting independent and additive effects of acute renal denervation and ANF on tubular reabsorption. The exaggerated response in the acutely denervated kidney can be explained by removal of a modulatory effect of the renal efferent nerves and associated increases in tubular flow and delivery to more distal ANF-sensitive sites. The denervation responses suggest that the renal efferent nerves have similar effects on sodium and water reabsorption in anesthetized SHR and WKY rats at 10-12 wk of age. The renal nerves and ANF appear to play a larger role in the acute control of sodium and water excretion in MW rats compared to rats of the Okamoto-Aoki strain.

scholarly journals Plasticity of pre- and postsynaptic GABAB receptor function in the paraventricular nucleus in spontaneously hypertensive rats

2008 ◽  
Vol 295 (2) ◽  
pp. H807-H815 ◽  
Author(s):  
De-Pei Li ◽  
Qing Yang ◽  
Hao-Min Pan ◽  
Hui-Lin Pan
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Brain Slices ◽  
Receptor Function ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Postsynaptic Currents ◽  
Wky Rats ◽  
Outward Currents ◽  
Bath Application ◽  
Shr And Wky Rats

GABAB receptor function is upregulated in the paraventricular nucleus (PVN) of the hypothalamus in spontaneously hypertensive rats (SHR), but it is unclear whether this upregulation occurs pre- or postsynaptically. We therefore determined pre- and postsynaptic GABAB receptor function in retrogradely labeled spinally projecting PVN neurons using whole cell patch-clamp recording in brain slices in SHR and Wistar-Kyoto (WKY) rats. Bath application of the GABAB receptor agonist baclofen significantly decreased the spontaneous firing activity of labeled PVN neurons in both SHR and WKY rats. However, the magnitude of reduction in the firing rate was significantly greater in SHR than in WKY rats. Furthermore, baclofen produced larger membrane hyperpolarization and outward currents in labeled PVN neurons in SHR than in WKY rats. The baclofen-induced current was abolished by either including G protein inhibitor GDPβS in the pipette solution or bath application of the GABAB receptor antagonist in both SHR and WKY rats. Blocking N-methyl-d-aspartic acid receptors had no significant effect on baclofen-elicited outward currents in SHR. In addition, baclofen caused significantly greater inhibition of glutamatergic excitatory postsynaptic currents (EPSCs) in labeled PVN neurons in brain slices from SHR than WKY rats. By contrast, baclofen produced significantly less inhibition of GABAergic inhibitory postsynaptic currents (IPSCs) in labeled PVN neurons in SHR than in WKY rats. Although microinjection of the GABAB antagonist into the PVN increases sympathetic vasomotor tone in SHR, the GABAB antagonist did not affect EPSCs and IPSCs of the PVN neurons in vitro. These findings suggest that postsynaptic GABAB receptor function is upregulated in PVN presympathetic neurons in SHR. Whereas presynaptic GABAB receptor control of glutamatergic synaptic inputs is enhanced, presynaptic GABAB receptor control of GABAergic inputs in the PVN is attenuated in SHR. Changes in both pre- and postsynaptic GABAB receptors in the PVN may contribute to the control of sympathetic outflow in hypertension.

scholarly journals Enhanced catabolism to acetaldehyde in rostral ventrolateral medullary neurons accounts for the pressor effect of ethanol in spontaneously hypertensive rats

2012 ◽  
Vol 302 (3) ◽  
pp. H837-H844 ◽  
Author(s):  
Mahmoud M. El-Mas ◽  
Abdel A. Abdel-Rahman
Keyword(s):  
Blood Pressure ◽  
Catalase Activity ◽  
Spontaneously Hypertensive Rats ◽  
Pressor Response ◽  
Critical Role ◽  
Ventrolateral Medulla ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Strain Dependent

We have previously shown that ethanol microinjection into the rostral ventrolateral medulla (RVLM) elicits sympathoexcitation and hypertension in conscious spontaneously hypertensive rats (SHRs) but not in Wistar-Kyoto (WKY) rats. In this study, evidence was sought to implicate the oxidative breakdown of ethanol in this strain-dependent hypertensive action of ethanol. Biochemical experiments revealed significantly higher catalase activity and similar aldehyde dehydrogenase (ALDH) activity in the RVLM of SHRs compared with WKY rats. We also investigated the influence of pharmacological inhibition of catalase (3-aminotriazole) or ALDH (cyanamide) on the cardiovascular effects of intra-RVLM ethanol or its metabolic product acetaldehyde in conscious rats. Compared with vehicle, ethanol (10 μg/rat) elicited a significant increase in blood pressure in SHRs that lasted for the 60-min observation period but had no effect on blood pressure in WKY rats. The first oxidation product, acetaldehyde, played a critical role in ethanol-evoked hypertension because 1) catalase inhibition (3-aminotriazole treatment) virtually abolished the ethanol-evoked pressor response in SHRs, 2) intra-RVLM acetaldehyde (2 μg/rat) reproduced the strain-dependent hypertensive effect of intra-RVLM ethanol, and 3) ALDH inhibition (cyanamide treatment) uncovered a pressor response to intra-RVLM acetaldehyde in WKY rats similar to the response observed in SHRs. These findings support the hypothesis that local production of acetaldehyde, due to enhanced catalase activity, in the RVLM mediates the ethanol-evoked pressor response in SHRs.

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