Molecular biology, endocrinology, and pharmacology of the cardiac renin-angiotensin system

Recent evidence for the existence of extrarenal tissue renin-angiotensin systems has raised the question whether such a system also exists in the heart. In this communication, we present evidence for a cardiac renin-angiotensin system based on molecular biological and biochemical data. In addition, we address the question whether the components of this system interact as a locally integrated, biologically functioning unit. 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, followed by the right and left ventricle. Using specific, HPLC-controlled RIAs for angiotensin peptides, we demonstrated the presence of both angiotensin I and angiotensin II in all anatomical regions of the monkey and rat heart. Similarly, the presence of converting enzyme activity was ascertained by direct in vitro determinations. Additional experiments evaluating the spontaneous release of angiotensinogen from isolated, perfused rat hearts revealed a bimodal pattern of high, but rapidly declining rates during the first hour (perhaps representing the washout of a pool sequestered from plasma), followed by a prolonged period of steady, low level release, consistent with the secretion of locally synthesized protein. In separate experiments aimed at examining the possible local integration of the components of the cardiac renin-angiotensin system, we measured angiotensin II concentrations in the coronary sinus effluent of isolated, perfused rat hearts. Infusion of angiotensin I resulted in the prompt appearance of angiotensin II, amounting to a single pass fractional conversion of 6.42 +/- 0.33%.(ABSTRACT TRUNCATED AT 250 WORDS)