Kininase-independent potentiation of endothelium-dependent relaxations to kinins by converting enzyme inhibitor perindoprilat.
OBJECTIVE
The present study examined whether or not the resistance to degradation of bradykinin analogs affects the kinin-potentiating action of the inhibitor of converting enzyme, perindoprilat.


METHODS
Hydrolysis of Hyp3,Tyr(Me)8 -bradykinin by ACE present in isolated canine coronary arteries was assessed by determination of peptide metabolites using electrospray mass spectrometry, and compared to that of bradykinin. Contractions and relaxations of isolated rings of coronary arteries, with and without endothelium, were recorded as changes in isometric force.


RESULTS
After a 30 min incubation, most of the bradykinin was degraded by the arteries, while less than 10 % of Hyp3,Tyr(Me)8 -bradykinin was hydrolysed. In organ chambers, Hyp3,Tyr(Me)8 -bradykinin like bradykinin caused relaxations of isolated canine coronary arteries with endothelium that could be attributed to both NO and endothelium-derived hyperpolarizing factor (EDHF). Perindoprilat caused a comparable leftward shift in the concentration-relaxation curves for bradykinin and Hyp3,Tyr(Me)8 -bradykinin.


CONCLUSIONS
Impairment of the degradation of bradykinin is not an essential mechanism by which perindoprilat potentiates the actions of kinins.
Mombouli
Jean-Vivien
JV
University of Marien Ngouabi, Brazzaville, Republic of Congo.
Ballard
Kevin D
KD
Vanhoutte
Paul M
PM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D001920:Bradykinin / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism / Q000502:physiology; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001685:Biological Factors; D007211:Indoles; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C067410:endothelium-dependent hyperpolarization factor; C053500:perindoprilat; D009569:Nitric Oxide; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin