AT 1 Receptor Antagonist Treatment Caused Persistent Arterial Functional Changes in Young Spontaneously Hypertensive Rats

Hypertension ◽  
1997 ◽  
Vol 30 (6) ◽  
pp. 1471-1478 ◽  
Author(s):  
Leesa K. Gillies ◽  
Mei Lu ◽  
Hong Wang ◽  
Robert M. K. W. Lee
Keyword(s):  
Receptor Antagonist ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Functional Changes

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.

Role of thromboxane in control of arterial pressure and renal function in young spontaneously hypertensive rats

1986 ◽  
Vol 250 (3) ◽  
pp. F488-F496 ◽  
Author(s):  
H. J. Grone ◽  
R. S. Grippo ◽  
W. J. Arendshorst ◽  
M. J. Dunn
Keyword(s):  
Renal Function ◽  
Arterial Pressure ◽  
Receptor Antagonist ◽  
Spontaneously Hypertensive Rats ◽  
Renal Plasma Flow ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Txa2 Receptor ◽  
Wistar Kyoto ◽  
Txa2 Receptor Antagonist

As platelet and renal thromboxane (TX)A2 synthesis are increased in spontaneously hypertensive rats (SHR), we tested the hypothesis that increased renal TXA2 synthesis may cause the reduction in glomerular filtration rate (GFR), renal plasma flow (RPF), and the increase in arterial pressure in SHR of the Okamoto-Aoki strain. A selective inhibitor of TXA2 synthetase (UK 38485) was given acutely, with or without a TXA2 receptor antagonist (EP-092), to 6- to 8-wk-old SHR and age-matched Wistar-Kyoto rats (WKY) and chronically for 5.5 wk to 3.5-wk-old SHR. Inhibition of TXA2, measured by the stable metabolite TXB2, in the acute experiments was greater than 95% in serum and greater than 80% in glomeruli; in the chronic studies, it was greater than 65% in glomeruli. There was no endoperoxide shunting to vasodilatory and natriuretic prostaglandins (PGE2, PGI2) in glomeruli after TXA2 inhibition. Before drug administration, GFR and RPF were reduced and renal vascular resistance (RVR) was increased in SHR. During acute blockade of renal TXA2 synthesis, with or without a TXA2 receptor antagonist, there was no significant change in GFR, RPF, or RVR in WKY and SHR. Inhibition of TXA2 did not affect urine flow or sodium excretion in anesthetized or conscious WKY or SHR. Mean arterial pressure did not fall in treated SHR and WKY. Chronic TXA2 synthesis inhibition did not improve GFR or RPF in SHR, and systolic arterial pressure was not altered. These findings show that enhanced serum and glomerular TXA2 synthesis do not significantly contribute to the reduction in renal function and are not essential for the development of hypertension in young SHR.

scholarly journals Angiotensin II AT1 Receptor Blockade Abolishes Brain Microvascular Inflammation and Heat Shock Protein Responses in Hypertensive Rats

2005 ◽  
Vol 25 (7) ◽  
pp. 878-886 ◽  
Author(s):  
Jin Zhou ◽  
Hiromichi Ando ◽  
Miroslava Macova ◽  
Jingtao Dou ◽  
Juan M Saavedra
Keyword(s):  
Angiotensin Ii ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Receptor Antagonist ◽  
Spontaneously Hypertensive Rats ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Cerebral Microvessels ◽  
Spontaneously Hypertensive

Endothelial dysfunction and inflammation enhance vulnerability to hypertensive brain damage. To explore the participation of Angiotensin II (Ang II) in the mechanism of vulnerability to cerebral ischemia during hypertension, we examined the expression of inflammatory factors and the heat shock protein (HSP) response in cerebral microvessels from spontaneously hypertensive rats and their normotensive controls, Wistar Kyoto rats. We treated animals with vehicle or the Ang II AT1 receptor antagonist candesartan, 0.3 mg/kg/day, via subcutaneously implanted osmotic minipumps for 4 weeks. Spontaneously hypertensive rats expressed higher Angiotensin II AT1 receptor protein and mRNA than normotensive controls. Candesartan decreased the macrophage infiltration and reversed the enhanced tumor necrosis factor-α and interleukin-1β mRNA and nuclear factor-κB in microvessels in hypertensive rats. The transcription of many HSP family genes, including HSP60, HSP70 and HSP90, and heat shock factor-1 was higher in hypertensive rats and was downregulated by AT1 receptor blockade. Our results suggest a proinflammatory action of Ang II through AT1 receptor stimulation in cerebral microvessels during hypertension, and very potent antiinflammatory effects of the Ang II AT1 receptor antagonist. These compounds might be considered as potential therapeutic agents against ischemic and inflammatory diseases of the brain.

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