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(Hypertension. 1995;25:288-293.)
© 1995 American Heart Association, Inc.

Articles

Enhanced Slow Pressor Effect of Angiotensin II in Two-Kidney, One Clip Rats

Matthew G. Melaragno; Gregory D. Fink

From the Department of Pharmacology and Toxicology, Michigan State University, East Lansing.

Correspondence to Gregory D. Fink, PhD, Department of Pharmacology and Toxicology, Michigan State University, B-327 Life Sciences Bldg, East Lansing, MI 48824.

Abstract Phase II of two-kidney, one clip (2K1C) Goldblatt hypertension in the rat is characterized by elevated blood pressure and near-normal plasma concentrations of angiotensin II (Ang II) but is reversed by inhibition of the renin-angiotensin system. We hypothesized that this angiotensin dependence is due to enhanced responsiveness to the slow pressor effect of Ang II caused by renal artery stenosis. To test this idea, we submitted rats to either renal artery clipping or sham operation. These groups were immediately subdivided; some animals received enalapril in their drinking water (508 µmol/L), and the rest drank distilled water only. After 10 to 14 days, catheters were inserted into the aorta and vena cava, and the rats were housed in metabolism cages. After 3 control days of measurement of mean arterial pressure and other variables, the enalapril-treated groups received an intravenous infusion of Ang II at a dose of 3.8 pmol/min (4 ng/min) for 14 days. Rats not drinking enalapril received only saline vehicle (2 mmol Na⁺ per day). After 3 days of Ang II infusion, the enalapril-treated 2K1C rats had attained a significantly higher level of mean arterial pressure than the enalapril-treated sham rats. At the end of the Ang II infusion, mean arterial pressure in enalapril-treated 2K1C rats was 151±6 mm Hg versus 107±7 mm Hg in enalapril-treated sham rats. Mean arterial pressure in the enalapril-treated sham rats after Ang II infusion was not significantly different from that of untreated sham rats (109±2 mm Hg). No significant differences in urinary sodium excretion or water balance were noted between the 2K1C and sham rats. These results support the hypothesis that 2K1C rats exhibit enhanced responsiveness to the slow pressor effect of Ang II.

Key Words: hypertension, renovascular • angiotensin II • rats

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