Effect of pH on the inhibition of angiotensin converting activity by enalaprilat in the rat perfused mesenteric vascular bed.
The previous finding that converting enzyme inhibitors (CEIs) potentiate bradykinin (BK), but do not inhibit conversion of angiotensin (ANG) I in isolated vessels, was explored further in the rat perfused mesenteric vascular bed. To investigate whether other peptidases besides angiotensin converting enzyme (ACE) might be involved in CEI-resistant ANG I conversion, synthetic angiotensinogen fragments (1-14, 1-11 and 2-14) were studied. Their vasoconstrictor activities were found to be about 80 times less than that of ANG I, and were not altered by the CEI enalaprilat, indicating that tonin-like enzymes do not play a role in the generation of ANG II by the arterial wall. The hypothesis that BK potentiation by CEI in arteries might be due to a direct effect on the receptors was not supported by the lack of potentiation, by enalaprilat, of the vasorelaxant effect of Lys-Lys-BK (an ACE-resistant BK homologue). Finally, the effect of pH in the perfusing solution on ACE inhibition by enalaprilat was studied. Whereas converting activity decreased with increasing pH in the range 6.8 to 8.1, enalaprilat did not affect the responses to ANG I at pH 7.5 or 7.8, but blocked them at pH 7.1. Our results indicate that arterial ACE shows substrate-specific inhibition and that, at physiological pH, converting activity is resistant to inhibition by CEIs, whose hypotensive action would be due mainly to inhibition of arterial wall kininase activity.
Lindsey
C J
CJ
Department of Biophysics, Escola Paulista de Medicina, São Paulo, Brazil.
Bendhack
L M
LM
Paiva
A C
AC
D000804:Angiotensin II / Q000096:biosynthesis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D004656:Enalapril / Q000031:analogs & derivatives* / Q000494:pharmacology; D015773:Enalaprilat; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000201:enzymology*; D008642:Mesenteric Veins / Q000201:enzymology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000804:Angiotensin II; D004656:Enalapril; D015773:Enalaprilat; D001920:Bradykinin