ANGIOTENSINASES RESTRICT LOCALLY GENERATED ANGIOTENSIN-II TO THE BLOOD-VESSEL WALL

We tested the hypothesis that angiotensinases limit the spillover of l ocally formed angiotensin II into the circulation. The release of angi otensin peptides from isolated rat hindquarters perfused with an artif icial medium was measured by high-performance liquid chromatography an d radioimmunoassay. The spontaneous release of angiotensins was increa sed by the angiotensinase inhibitors phenanthroline (850+/-195 versus 95+/-33 fmol of angiotensin I per 30 minutes in controls, P<.05, n=5 e ach) and amastatin (P<.05, n=5 each). Infusion of renin induced sustai ned local angiotensin I formation, which was also increased by phenant hroline. Stimulation of local angiotensin formation by renin infusion was compared with infusion of exogenous angiotensin II. Renin caused s imilar increases of perfusion pressure (11.1+/-2.2 versus 7.6+/-1.9 mm Hg after angiotensin II, P>.05) despite lower angiotensin II levels i n the venous effluent than during infusion of exogenous angiotensin II (65+/-2 versus 482+/-33 fmol/mL, P<.05, n=7 each). Thus, renin must h ave caused higher angiotensin II tissue levels than indicated by the m easurements in the venous effluent. The presser response to renin was abolished by the type 1 angiotensin II receptor antagonist losartan. W e conclude that the major part of locally generated angiotensins is no t released into the circulation but degraded by angiotensinases within the tissue compartment.