Kallikrein potentiation of angiotensin I-induced contraction on isolated mesenteric artery.
The hypotheses that glandular kallikrein (KK) potentiate the conversion of angiotensin I (AI) to angiotensin II (AII) was tested on isolated mesenteric artery from rabbit. Cumulative additions of A1 in concentrations 10(-8), 5 X 10(-8) and 10(-7) M gave dose-related contractions of the artery. Due to tachyphylaxis second dose-response run was used for comparison. KK, 0.4 U/ml, potentiated these contractions. Addition of captopril (C, 10(-5) M) to inhibit angiotensin converting enzyme (ACE) reduced the AI responses markedly and tachyphylaxis almost completely. The responses of the KK induced potentiation of AI was the same regardless of the presence of captopril. KK, 0.01 U/ml or 0.4 U/ml, produced the same effects. Saralasin (S, 10(-5) M), an AII receptor antagonist, completely abolished the responses following C+KK+AI. Thus, these results indicate that the KK induced potentiation of the AI response is due to a conversion to AII. Bradykinin (BK, 10(-7), 10(-5) M) did not mimic the KK potentiation of AI. Three different kallikrein inhibitors, S-2441 (H-D-Pro-Phe-Arg-NH-heptyl X 2HCl), Trasylol and amiloride, reduced the KK potentiation of AI. Phentolamine, an alpha-adrenergic receptor antagonist added for inhibition of AII adrenergic facilitation, also reduced the KK induced potentiation of AI. In conclusion, these results indicate that KK potentiate the conversion of AI to AII and thereby induces vasopressor effects.
D000803:Angiotensin I / Q000494:pharmacology*; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004357:Drug Synergism; D007610:Kallikreins / Q000494:pharmacology*; D008638:Mesenteric Arteries; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D012504:Saralasin / Q000494:pharmacology; D013552:Swine; D013722:Teprotide
D000809:Angiotensins; D009842:Oligopeptides; D000803:Angiotensin I; D002216:Captopril; D013722:Teprotide; D007610:Kallikreins; D012504:Saralasin; D001920:Bradykinin