ARTERIAL RESPONSES TO BRADYKININ AFTER RAMIPRIL THERAPY IN EXPERIMENTAL-HYPERTENSION

Angiotensin-converting enzyme inhibitors have been shown to potentiate relaxations to kinins in several arteries, but the effects of long-te rm therapy on the responses to bradykinin in normotensive and hyperten sive animals remain largely unknown. Therefore, the effects of 12-week -long ramipril therapy (1 mg kg(-1) day(-1)) on responses of mesenteri c arterial rings in vitro were studied in spontaneously hypertensive r ats and normotensive Wistar-Kyoto rats. Endothelium-dependent relaxati ons of noradrenaline-precontracted rings to acetylcholine were similar in normotensive rats and ramipril-treated hypertensive rats and more pronounced than in untreated hypertensive group. Higher concentrations of bradykinin (0.1-1 mu M) induced slight contractions in noradrenali ne-precontracted endothelium-intact rings of normotensive groups and u ntreated hypertensive group, whereas no response or a transient relaxa tion were observed in ramipril-treated hypertensive rats. Interestingl y in ramipril-treated hypertensive rats but not in the other groups, 2 0-min. pretreatment of arterial rings with ramiprilat unmasked or pote ntiated the relaxations to bradykinin, and these bradykinin-induced re laxations were effectively inhibited by the B-2-kinin receptor antagon ist Hoe-140. In conclusion, ramipril treatment clearly improved endoth elium-dependent arterial relaxation to acetylcholine, and potentiated of even unmasked the dilatory response mediated via the endothelial B- 2-kinin receptor in spontaneously hypertensive rats. Since these enhan cing effects on arterial relaxation in vitro could not be attributed t o reduced breakdown of bradykinin, the present results suggest that lo ng-term angiotensin-converting enzyme inhibition potentiated the actio ns of kinins at level of B-2-kinin receptors.