Role of kinins in the acute antihypertensive effect of enalapril in hypertensive rats.
1. We used the kinin antagonist HOE 140 to investigate the role of endogenous kinins in the acute antihypertensive effect of the angiotensin converting enzyme inhibitor enalapril in chronic and acute renal hypertensive rats. 2. In normotensive rats, treatment with HOE 140 (33 micrograms/kg, sc) caused a complete blockade of the depressor effect of bradykinin (100 ng, ia) without affecting the depressor effect of sodium nitroprusside (1 microgram, i.v.) or the basal blood pressure. 3. HOE 140 treatment (33 micrograms/kg, sc, plus 330 ng/min, i.v.) did not affect basal blood pressure of chronic (6-7 weeks) one-kidney, one clip and two-kidney, one clip hypertensive rats and in rats with acute hypertension, elicited by unclamping the renal pedicle that had been occluded for 5 h, but HOE 140 completely blocked the hypotensive response to bradykinin (100 ng, ia) during the 60-min period after enalapril administration (2 mg/kg, i.v.). 4. Acutely hypertensive rats treated or not with HOE 140 (33 micrograms/kg, sc, plus 330 ng/min, i.v.) presented a similar fall in blood pressure after enalapril (165 +/- 5 to 137 +/- 6 mmHg and 166 +/- 5 to 136 +/- 6 mmHg, respectively). 5. Untreated two-kidney, one clip hypertensive rats presented a rapid and sustained fall in blood pressure after enalapril (177 +/- 4 to 148 +/- 4 mmHg) that did not differ from the HOE 140-treated (33 micrograms/kg, sc, plus 330 ng/min, i.v.) group (177 +/- 6 to 154 +/- 4 mmHg). 6. One-kidney, one clip hypertensive rats treated with HOE 140 (33 micrograms/kg, sc, plus 330 ng/min, i.v.) showed a significantly smaller fall in blood pressure after enalapril (204 +/- 7 to 179 +/- 9 mmHg) compared to the untreated rats (197 +/- 7 to 149 +/- 2 mmHg). 7. These results indicate that kinin potentiation plays an important role in the antihypertensive effect of acutely administered angiotensin converting enzyme inhibitor in the one-kidney, one clip model of hypertension.
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Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil.
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D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006977:Hypertension, Renal / Q000188:drug therapy*; D007705:Kinins / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D004656:Enalapril; C065679:icatibant; D001920:Bradykinin