Conversion and degradation of [125I] labelled angiotensin I in isolated perfused porcine coronary and carotid arteries.

OBJECTIVE

The aims were (1) to quantitate angiotensin I to II conversion on the endothelial surface and at deeper sites in isolated arteries, (2) to assess whether the angiotensin II that is formed at deeper sites is released into the vascular lumen, and (3) to examine whether enzymes other than angiotensin converting enzyme (ACE) are involved in vascular angiotensin I to II conversion.

METHODS

Metabolism of [125I]-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 absence of captopril.

RESULTS

[125I]-angiotensin II was a major metabolite and its formation was virtually completely blocked by captopril, after both luminal and adventitial administration of [125I]-angiotensin I. In coronary arteries (n = 8), the [125I]-angiotensin I to II conversion rate after adventitial administration was about half that after luminal administration. In coronary arteries (n = 6) the conversion rate after adventitial administration was 10-20 times lower than after luminal administration. Degradation of [125I]-angiotensin I into peptides other than [125I]-angiotensin II was also observed, with both luminal and adventitial administration. No [125I]-angiotensin I or II was released into the organ bath after luminal administration of [125I]-angiotensin I, and very little [125I]-angiotensin I and II entered the lumen after adventitial administration of [125I]-angiotensin I.

CONCLUSIONS

(1) Vascular angiotensin I to II conversion is not limited to the endothelial surface. (2) ACE is the most important, if not the only, enzyme responsible for vascular angiotensin I to II conversion. (3) If angiotensin I and II are formed in the adventitia or media, little of these peptides will enter the vascular lumen.