Inhibitors of peptidases: how they influence the biological activities of substance P, neurokinins, kinins and angiotensins in isolated vessels.
Myotropic effects of various peptides were measured in three isolated vessels, the dog carotid artery, the rabbit pulmonary artery and the rat portal vein in the absence and in presence of several peptidase inhibitors, in order to evaluate the interference by metabolism with the peptides' biological activities. After adequate controls, captopril (4.6 x 10(-6) mol/l), thiorphan (1.0 x 10(-6) mol/l), phosphoramidon (4.6 x 10(-6) mol/l), chymostatin (1 mg/l), bestatin (8.1 x 10(-6) mol/l) or bacitracin (1.4 x 10(-5) mol/l) were left in contact with the tissues for 20-40 min to inhibit tissue peptidases before measuring again the biological effects of the various peptides. In some experiments, mergetpa (5.4 x 10(-6) mol/l) was used. All peptidase inhibitors were inactive on their own and only captopril potentiated the effects of substance P, neurokinins, bradykinin and inhibited angiotensin I in two preparations, the dog carotid artery, the rat portal vein, and, excluding bradykinin, also in the rabbit pulmonary artery. Captopril and thiorphan significantly potentiated the maximal response of the rat portal vein to substance P and mergetpa inhibited completely the effect of bradykinin on the rabbit pulmonary artery. The present findings suggest that the most active proteolytic enzyme interfering with the biological effects of vasoactive peptides on three isolated vessels is the angiotensin-converting enzyme (kininase II).
Department of Pharmacology, Medical School, University of Sherbrooke, Que., Canada.
N
N
Rouissi
F
F
Nantel
G
G
Drapeau
N E
NE
Rhaleb
S
S
Dion
D
D
Regoli
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007705:Kinins / Q000037:antagonists & inhibitors*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015288:Neurokinin A / Q000037:antagonists & inhibitors; D015287:Neurokinin B / Q000037:antagonists & inhibitors; D011169:Portal Vein / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000037:antagonists & inhibitors*
D007705:Kinins; D011480:Protease Inhibitors; D000804:Angiotensin II; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D002216:Captopril; D007930:Leucine; C012211:ubenimex