Kinin antagonist reverses converting enzyme inhibitor-stimulated vascular prostaglandin I2 synthesis.
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.
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Hypertension Research Division, Henry Ford Hospital, Detroit, Michigan 48202.
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D015773:Enalaprilat; D011464:Epoprostenol / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism; D007705:Kinins / Q000037:antagonists & inhibitors*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D011453:Prostaglandins; C053748:B 4162; D004656:Enalapril; D002216:Captopril; D011464:Epoprostenol; D015773:Enalaprilat; D001920:Bradykinin