Cardiac renin-angiotensin system

Abstract

Based on molecular, biological, biochemical, and pharmacological data, evidence is presented for a cardiac renin-angiotensin system. Using radiolabeled cRNA probes prepared from specific cDNA fragments, we were able to document renin and angiotensinogen gene expression in atria and ventricles of the rat heart by Northern blot and liquid hybridization analysis. Relative signal strength for both mRNAs was highest in the atria and next highest in the right and left ventricle. We also demonstrated the presence of both angiotensin I and angiotensin II in all anatomical regions of the monkey and rat heart using specific, high pressure liquid chromatography (HPLC) controlled radioimmunoassays (RIAs) for angiotensin peptides. The presence of converting-enzyme activity was also ascertained by direct in vitro determinations. Infusion of angiotensin I into the isolated perfused rat heart resulted in the prompt appearance of angiotensin II; the single pass fractional conversion was 6.42 +/- 0.33%. Dose-dependent inhibition of this effect by simultaneous infusion of converting-enzyme inhibitor supports the existence of a specific intracardiac pathway for the activation of angiotensin II. When the isolated, perfused rat hearts were exposed to infusions of purified renin, angiotensin I, undetectable before renin, was dose-dependently released into the coronary circulation at peak rates ranging from 2.4 +/- 0.7 fmol/min to 1.4 +/- 0.2 pmol/min, of which 7.2 +/- 1.1% was intracardially converted to angiotensin II. All renin effects were blocked in the presence of a specific pentapeptide renin inhibitor. Together, the results of these studies add support to the concept of a functionally active cardiac tissue renin-angiotensin system.