title: Kininases and vascular responses to kinins.
abstract: We have utilized several inhibitors to assess the effects of kininases on the contractile activity of bradykinin (BK), kallidin (KD), des-Arg9-BK and des-Arg10-KD on two isolated blood vessels, the rabbit aorta and mesenteric vein. The response of the two vessels to kinins are mediated by B1-receptors, implying that fragments of kinins without the C-terminal arginine are much more active on these tissues than the whole kinin sequences. Blockers of carboxypeptidase B-like enzymes, such as SQ24798 and pivalyl-L-arginine decrease the apparent affinity of BK and KD on the two vessels, while not changing those of des-Arg9-BK and des-Arg10-KD; this suggests that a major part of the contractile activities of BK and KD are mediated by des-Arg metabolites formed in situ at the tissue level by a kininase I. The block of kininase II by captopril or desacetylated MK-421 bring about a complex pattern of activity changes that include the potentiation of BK and KD and the depression of des-Arg10-KD. These results, in conjunction with those obtained with the non-specific inhibitors of metallopeptidases, thioglycolic acid and EDTA, suggest that the relative contribution of kininase I and kininase II to the degradation of kinins in arterial and venous vessels may be different. The implications of these findings on the pharmacology of B1-receptors are discussed.
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001920:Bradykinin / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology; D002268:Carboxypeptidases / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007705:Kinins / Q000494:pharmacology*; D001121:Lysine Carboxypeptidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011817:Rabbits; D018002:Receptors, Bradykinin; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D018002:Receptors, Bradykinin; D011956:Receptors, Cell Surface; D002216:Captopril; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase; D001920:Bradykinin