Degradation of angiotensin I in the endothelium and smooth muscle of the rat aorta.
In homogenates of the endothelium and smooth muscle cum adventitia of the rat aorta, exogenous angiotensin (ANG) I was found to be degraded to des-aspartate-ANG I (des-Asp-ANG I) instead of ANG II. ANG II and ANG III were not detectable in either of the homogenates after 5, 10 and 30 min of incubation with the decapeptide. However, both the homogenates were able to catalyse hippuryl-L-histidyl-L-leucine (HHL) to hippuric acid and the catalysis was completely inhibited by 3 microM captopril. The data show that the angiotensin converting enzyme (ACE) present in the homogenates of rat aorta, prepared by normal laboratory procedures, is not able to hydrolyse ANG I to ANG II. This finding has important consequences in the study of vascular ACE as the assay of the enzyme is often carried out using crude homogenate and HHL or other artificial substrates. In addition, the aminopeptidase that degraded ANG I to des-Asp-ANG I was not inhibited by either amastatin or bestatin, indicating that it was not aminopeptidase A or B. Together with the recent findings of other investigators which show that the de novo production of ANG II in vascular tissues is stimulated and inhibited by beta- and alpha-agonists, respectively, our present data may suggest that production of vascular ANG II occurs only in intact tissues and is probably under adrenergic regulation.
Sim
M K
MK
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000805:Angiotensin III / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents; D001011:Aorta / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D010455:Peptides; D000804:Angiotensin II; D000805:Angiotensin III; C016977:amastatin; D000803:Angiotensin I; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex