Vascular Production and Regulation of Angiotensin

Abstract

To test the hypothesis that angiotensin (Ang) I and II are produced by blood vessels, we investigated the formation of both Ang I and Ang II in isolated, perfused rat hindquarters. To characterize the nature of this production further, we modulated plasma renin by total or subtotal nephrectomy and tested the effects of exogenous renin and renin substrate on vascular Ang formation. Assays of the perfusate by high-performance liquid chromatography and radioimmunoassay demonstrated the spontaneous release of Ang I and Ang II from the hindlimb vasculature. Conversion of Ang I to Ang II in hindquarter vasculature was approximately 75% and was totally suppressed by captopril. The spontaneous formation of Ang peptides was abolished by bilateral nephrectomy but was not affected by subtotal 5/6 nephrectomy. The addition of purified rat angiotensinogen to the preparation increased Ang II levels. The infusion of renin into the hindlimb vasculature led to substantial increases in local Ang formation and also raised the perfusion pressure. Both effects were sensitive to captopril and to the renin inhibitor H-142. The data indicate that Ang I and Ang II are produced locally within blood vessels. However, the origin of vascular renin remains controversial. Our results suggest that part of the enzyme is taken up from plasma.