RENIN-ANGIOTENSIN SYSTEM COMPONENTS IN THE INTERSTITIAL FLUID OF THE ISOLATED-PERFUSED RAT-HEART - LOCAL PRODUCTION OF ANGIOTENSIN-I

We used a modification of the isolated perfused rat heart, in which co ronary effluent and interstitial transudate were separately collected, to investigate the uptake and clearance of exogenous renin, angiotens inogen, and angiotensin I (Ang I) as well as the cardiac production of Ang I. The levels of these compounds in interstitial transudate were considered to be representative of the levels in the cardiac interstit ial fluid. During perfusion with renin or angiotensinogen, the steady- state levels (mean +/- SD) in interstitial transudate were 64 +/- 34% (P<.05 for difference from the arterial level, n=8) and 108 +/- 42% (n =6) of the arterial level, respectively; the levels in coronary efflue nt were not significantly different from those in interstitial transud ate. Ang I was not detectable in interstitial transudate during perfus ion with Tyrode's buffer or angiotensinogen. It was very low in inters titial transudate during perfusion with renin and rose to much higher levels during combined renin and angiotensinogen perfusion. The total production rate of Ang I present in interstitial fluid could be largel y explained by the renin-angiotensinogen reaction in the fluid phase o f the interstitial compartment. In contrast, the total production rate of Ang I present in coronary effluent and the net ejection rate of An g I via coronary effluent were, respectively, 4.6 +/- 2.2 and 2.8 +/- 1.3 (P<.01 and P<.05 for difference from 1.0, n=6) times higher than c ould be explained by Ang I formation in the fluid phase of the intrava scular compartment. Ang I from the interstitial fluid contributed litt le to the Ang I in the intravascular fluid and vice versa. These data reveal two tissue sites of Ang I production, ie, the interstitial flui d and a site closer to the blood compartment, possibly vascular surfac e-bound renin. There was no evidence that the release of locally produ ced Ang I into coronary effluent and interstitial transudate occurred independently of blood-derived renin or angiotensinogen.