CONVERSION AND DEGRADATION OF [I-125] LABELED ANGIOTENSIN-I IN ISOLATED-PERFUSED PORCINE CORONARY AND CAROTID ARTERIES

Objective: The aims were (1) to quantitate angiotensin I to II convers ion on the endothelial surface and at deeper sites in isolated arterie s, (2) to assess whether the angiotensin II that is formed at deeper s ites is released into the vascular lumen, and (3) to examine whether e nzymes other than angiotensin converting enzyme (ACE) are involved in vascular angiotensin I to II conversion. Methods: Metabolism of [I-125 ]-angiotensin I was studied in isolated perfused porcine coronary and carotid arteries after luminal administration of the labelled peptide (in the perfusion fluid) and after adventitial administration (in the organ bath). Measurements were made both in the presence and in the ab sence of captopril. Results: [I-125]-angiotensin II was a major metabo lite and its formation was virtually completely blocked by captopril, after both luminal and adventitial administration of [I-125]-angiotens in I. In coronary arteries (n = 8), the [I-125]-angiotensin I to II co nversion rate after adventitial administration was about half that aft er luminal administration. In coronary arteries (n = 6) the conversion rate after adventitial administration was 10-20 times lower than afte r luminal administration. Degradation of [I-125]-angiotensin I into pe ptides other than [I-125]-angiotensin II was also observed, with both luminal and adventitial administration. No [I-125]-angiotensin I or II was released into the organ bath after luminal administration of [I-1 25]-angiotensin I, and very little [I-125]-angiotensin I and II entere d the lumen after adventitial administration of [I-125]-angiotensin I. Conclusions: (1) Vascular angiotensin I to II conversion is not limit ed to the endothelial surface. (2) ACE is the most important, if not t he only, enzyme responsible for vascular angiotensin I to II conversio n. (3) If angiotensin I and II are formed in the adventitia or media, little of these peptides will. enter the vascular lumen.