Angiotensin II Type 1 Receptor–Mediated Augmentation of Urinary Excretion of Endogenous Angiotensin II in Val5-Angiotensin II–Infused Rats

Rats infused chronically with Val-Angiotensin (Ang) II exhibit increased urinary excretion of endogenous Ile-Ang II by the 12th day of infusion, suggesting the stimulation of endogenous Ang II formation by Val-Ang II infusion. The present study determined the time course of increased urinary Ang II...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2010-09, Vol.56 (3), p.378-383
Main Authors: Shao, Weijian, Seth, Dale M, Navar, L. Gabriel
Format: Article
Language:English
Subjects:
Analysis of Variance
Angiotensin II - pharmacology
Angiotensin II - urine
Angiotensin II Type 1 Receptor Blockers - pharmacology
Animals
Arterial hypertension. Arterial hypotension
Benzimidazoles - pharmacology
Biological and medical sciences
Blood and lymphatic vessels
Blood Pressure - drug effects
Cardiology. Vascular system
Chromatography, Liquid
Clinical manifestations. Epidemiology. Investigative techniques. Etiology
Hypertension, Renal - chemically induced
Hypertension, Renal - metabolism
Hypertension, Renal - physiopathology
Kidney - drug effects
Kidney - metabolism
Male
Medical sciences
Radioimmunoassay
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1 - metabolism
Renin-Angiotensin System - drug effects
Tetrazoles - pharmacology
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Summary:Rats infused chronically with Val-Angiotensin (Ang) II exhibit increased urinary excretion of endogenous Ile-Ang II by the 12th day of infusion, suggesting the stimulation of endogenous Ang II formation by Val-Ang II infusion. The present study determined the time course of increased urinary Ang II excretion and the effects of Ang II type 1 receptor blockade (candesartan, 2 mg/kg per day) on the urinary excretion rates of Ile-Ang II in Val-Ang II–infused (80 ng/min) rats. Ile-Ang II was separated from Val-Ang II by high-performance liquid chromatography and measured by radioimmunoassay. Systolic blood pressure increased progressively (215±2 mm Hg) in Val-Ang II–infused rats (n=5), whereas the candesartan-treated group (n=6) remained normotensive (124±3 mm Hg). Candesartan treatment significantly increased the level of plasma Ile-Ang II (24.0±7.6 versus 156.9±24.6 fmol/mL; P
ISSN:0194-911X
1524-4563
DOI:10.1161/HYPERTENSIONAHA.110.153106