Kininases and vascular responses to kinins

Eur J Pharmacol. 1982 Feb 26;78(2):167-74. doi: 10.1016/0014-2999(82)90233-3.


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

  • Angiotensin-Converting Enzyme Inhibitors
  • Animals
  • Aorta, Thoracic / drug effects
  • Bradykinin / metabolism
  • Captopril / pharmacology
  • Carboxypeptidases / metabolism*
  • Female
  • In Vitro Techniques
  • Kinins / pharmacology*
  • Lysine Carboxypeptidase / antagonists & inhibitors
  • Lysine Carboxypeptidase / metabolism*
  • Male
  • Mesenteric Veins / drug effects
  • Muscle Contraction / drug effects*
  • Muscle, Smooth, Vascular / drug effects*
  • Peptidyl-Dipeptidase A / metabolism*
  • Rabbits
  • Receptors, Bradykinin
  • Receptors, Cell Surface / metabolism*


  • Angiotensin-Converting Enzyme Inhibitors
  • Kinins
  • Receptors, Bradykinin
  • Receptors, Cell Surface
  • Captopril
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • Lysine Carboxypeptidase
  • Bradykinin