Hypertension, Vol 20, 74-79, Copyright © 1992 by American Heart Association
G Bao, P Gohlke, F Qadri and T Unger
The contribution of endogenous kinins to the chronic antihypertensive
effect of angiotensin converting enzyme inhibitors was investigated in
two-kidney, one clip hypertensive Wistar rats, using the new bradykinin
B2-receptor antagonist HOE 140 (D-Arg, [Hyp3, Thi5, D-Tic7, Oic8]-
bradykinin). In a first protocol, rats were pretreated orally with the
angiotensin converting enzyme inhibitor ramipril (1 mg/kg per day), for 4
weeks. Acute blockade of bradykinin receptors by intravenous injections of
HOE 140 at doses of 8.4 and 100 micrograms/kg, which inhibited the
depressor responses to exogenous bradykinin, did not affect the
antihypertensive effect of ramipril in these animals. Bradykinin receptors
were then blocked chronically by subcutaneous infusion of HOE 140 (500
micrograms/kg per day) via osmotic minipumps for 6 weeks, while ramipril
treatment was continued. HOE 140 partially reversed the antihypertensive
effect of ramipril from 115.3 +/- 4.6 to 123.8 +/- 3.3 mm Hg (mean arterial
blood pressure) after 3 weeks and to 121.3 +/- 2.9 mm Hg after 6 weeks. In
contrast, in controls (ramipril plus subcutaneous vehicle infusion) mean
arterial blood pressure decreased further from 112.0 +/- 6.0 to 110.3 +/-
4.9 mm Hg after 3 weeks and to 103.7 +/- 5.0 mm Hg after 6 weeks (p less
than 0.05 and p less than 0.01, HOE 140 versus controls). Plasma
catecholamines were not significantly different between the two groups at
the end of the experiment, indicating that the partial reversal of the
antihypertensive effect was not due to a bradykinin-like agonistic effect
on catecholamine release.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Chronic kinin receptor blockade attenuates the antihypertensive effect of ramipril
Department of Pharmacology, University of Heidelberg, FRG.
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