Hypertension, Vol 13, 754-758, Copyright © 1989 by American Heart Association
WH Beierwaltes and OA Carretero
Treatment with a converting enzyme inhibitor has been shown to stimulate
aortic prostaglandin I2 synthesis. We studied whether converting enzyme
inhibitor-stimulated prostaglandin I2 synthesis might be mediated by
kinins. Anesthetized male Sprague-Dawley rats were given a continuous
70-minute infusion of either saline or a kinin analogue antagonist,
[DArg0-Hyp3-Thi5-DPhe7-Thi8]bradykinin, 8 micrograms/kg/min. After 10
minutes, rats were given an intravenous bolus of either vehicle or the
converting enzyme inhibitor enalaprilat (30 micrograms/100 g body wt).
After 70 minutes, aorta and renal cortical slices were harvested and
incubated in vitro in buffer without drugs at pH 7.4, 37 degrees C for 60
minutes. The buffer was then sampled for measurement of 6-keto
prostaglandin F1 alpha (an index of prostaglandin I2), prostaglandin E2,
and renin release (angiotensin I generation) by radioimmunoassay. The
aortic prostaglandin I2 from rats treated with converting enzyme inhibitor
was significantly elevated (36.7 +/- 5.0 ng/mg dry wt/hr) compared with
aorta from rats treated with either vehicle (25.6 +/- 2.2 ng/mg/hr), kinin
antagonist (25.1 +/- 2.4 ng/mg/hr), or kinin antagonist plus converting
enzyme inhibitor (23.0 +/- 2.0 ng/mg/hr), p less than 0.02. There were no
differences in aortic prostaglandin E2, renin release, or prostaglandin E2
from renal cortical slices. Direct in vitro incubation of aorta with molar
concentrations of converting enzyme inhibitor from 10(-9) to 10(-4) had no
effect on prostaglandin I2. These results suggest that kinins may mediate
the effect of converting enzyme inhibition on aortic prostaglandin I2
synthesis and thereby may account for part of the hemodynamic responses
resulting from treatment using converting enzyme inhibitors.
ARTICLES
Kinin antagonist reverses converting enzyme inhibitor-stimulated vascular prostaglandin I2 synthesis
Hypertension Research Division, Henry Ford Hospital, Detroit, Michigan 48202.
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