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)

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.

β-Pro7Ang III is a novel highly selective angiotensin II type 2 receptor (AT2R) agonist, which acts as a vasodepressor agent via the AT2R in conscious spontaneously hypertensive rats

2015 ◽  
Vol 129 (6) ◽  
pp. 505-513 ◽  
Author(s):  
Mark Del Borgo ◽  
Yan Wang ◽  
Sanja Bosnyak ◽  
Morimer Khan ◽  
Pia Walters ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Angiotensin Ii ◽  
Protein Binding ◽  
Binding Site ◽  
Spontaneously Hypertensive Rats ◽  
Protective Effects ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

We have synthesized a highly selective compound that is able to target a protein-binding site [called angiotensin (Ang) II type 2 receptor, AT2R] in the cardiovascular system. This research tool will enhance our ability to stimulate AT2R to produce protective effects against cardiovascular disease.

Abstract 11003: Hypothalamic Activated Microglia With Morphological Changes Accelerate Blood Pressure Elevation During the Hypertension Development Phase in Stroke-prone Spontaneously Hypertensive Rats

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ko Takesue ◽  
Takuya Kishi ◽  
Yoshitaka Hirooka
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Development Phase ◽  
Hypertensive Rats ◽  
Blood Pressure Elevation ◽  
Spontaneously Hypertensive ◽  
Activated Microglia ◽  
Wky Rats ◽  
Pressure Elevation ◽  
Hypertension Development

Introduction: A recent paradigm shift in cardiovascular pathophysiology is the impact of inflammation on hypertension. Inflammation within the paraventricular nucleus of the hypothalamus (PVN) is an important pathology of sympathetic hyperactivity, and is mainly mediated by innate immune cells, microglia. Activated microglia with alteration of their morphology produce inflammatory cytokines. Previous reports demonstrated that microglia within the PVN have activated morphology in angiotensin II-induced hypertensive rats and spontaneously hypertensive rats compared with normotensive control Sprague-Dawley rats or Wistar-Kyoto (WKY) rats. However, the role of activated microglia in the PVN in blood pressure elevation associated with sympathetic hyperactivity remains unknown. In the present study, we determined whether inhibition of microglial activation within the PVN attenuates the blood pressure elevation in genetically hypertensive rats. Methods and Results: We evaluated the activation of PVN microglia, identified by microglia specific ionized calcium-binding adaptor molecule 1 immunoreactivity, by measuring the roundness and the perimeter of microglia at 6 weeks of age, early hypertension development phase in stroke-prone spontaneously hypertensive rats (SHRSP) and compared with them in age-matched normotensive WKY rats. At 6 weeks of age, increased roundness and shortening of perimeter of microglia, indicating activated microglia, were observed in SHRSP compared with those in WKY rats. Then, we performed intracerebroventricular (ICV) administration of minocycline (5 μg/h) to deactivate microglia at 6 weeks of age for 4 weeks. ICV administration of minocycline significantly attenuated systolic blood pressure elevation in SHRSP over 4 weeks (at the end of experiments; 203.2±2.2 mm Hg vs. 215.9±2.7 mm Hg, n=8-9, P<0.05), but not in WKY rats. At 10 weeks of age, morphological analysis revealed that ICV minocycline significantly decreased the roundness and increased the perimeter of microglia, indicating deactivation of microglia, within the PVN in SHRSP. Conclusions: Hypothalamic activated microglia with morphologic changes accelerate blood pressure elevation during the hypertension development phase in SHRSP.

Abstract P150: Sex Difference of Hypertension in Spontaneously Hypertensive Rats: Role of Mitochondrial Oxidative Stress

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Rodrigo O Maranon ◽  
Carolina Dalmasso ◽  
Chetal N Patil ◽  
Jane F Reckelhoff
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Sex Difference ◽  
Spontaneously Hypertensive Rats ◽  
Pressor Response ◽  
Premenopausal Women ◽  
Hypertensive Rats ◽  
Mitochondrial Oxidative Stress ◽  
Spontaneously Hypertensive ◽  
Mitochondrial Superoxide

Men have higher blood pressure (BP) than premenopausal women. Pressor response to oxidative stress may be a major contributor to the sex difference in BP control. Mitochondrial oxidative stress is associated with hypertension; however, whether mitochondrial oxidative stress plays a role in the sex difference in BP is unknown. In the present study, we tested the hypothesis that mitochondrial oxidative stress contributes to the sex difference in BP regulation in spontaneously hypertensive rats (SHR). Young intact (iYMSHR) and castrated males (cYMSHR), and females SHR (YFSHR) (3 mos of age) were implanted with radiotelemeters, and after a 4 day baseline BP, were treated with mitoTempo (0.75 mg/kg/d, sc minipumps), a specific scavenger of mitochondrial superoxide, for 7 days. Following 10 days washout of mito-tempo, rats were treated with Tempol (30 mg/kg/day, po drinking water) for 7 days. iYMSHR have higher blood pressure (by telemetry) than cYMSHR and YFSHR (148±1 mmHg, n=5, vs 132±1 mmHg, n=5, and 139±1 mmHg, n=5; p<0.01, respectively). MitoTempo reduced BP by 6% in iYMSHR (147±1 vs 139±1, n=5; p<0.05) compared to females (3%: 139±1 vs 136±1; n=5; p: NS) and castrated males (4.5%: 132±1 vs 126±1, n=5; p<0.05). After 10 days washout, tempol reduced BP only in iYMSHR (144±1 vs 130±1 mmHg, n=5; p<0.05). Our results suggest that mitochondrial oxidative stress may contribute to BP regulation in male SHR, but has no effect in females. The data also suggest that the presence of testosterone is necessary for the pressor response to oxidative stress in males since Tempol had no effect on BP in castrated males. Further studies examining the effect of steroid hormones and mitochondria in BP regulation are necessary to elucidate the importance of mitochondrial oxidative stress on sex difference of hypertension.

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.

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