EVIDENCE FOR THE EXISTENCE OF A FUNCTIONAL CARDIAC RENIN-ANGIOTENSIN SYSTEM IN HUMANS

Background The presence of mRNA for the essential components of the re nin-angiotensin system (RAS) has been found in animal and human hearts . The present study was designed to provide evidence for the existence of a (functional) cardiac RAS. Methods and Results Twenty-four patien ts with atypical chest pain undergoing coronary angiography for diagno stic purposes were investigated. The cardiac production rate of angiot ensins was estimated by measurement of the cardiac extraction of I-125 -angiotensin I and I-125-angiotensin II associated with the determinat ion of endogenous angiotensins in aortic and coronary sinus blood in n ormal, low, or high sodium diets. In a normal sodium diet, angiotensin I and II aorta-coronary sinus gradients were tendentially negative (- 1.8+/-2.5 and -0.9+/-1.7 pg/mL, respectively), and the amounts of angi otensin I and II added by cardiac tissues were 6.5+/-3.1 and 2.7+/-1.3 pg/mL, respectively. The low sodium diet caused a significant increas e in both plasma renin activity (PRA) and angiotensin I concentration in aortic but not in coronary sinus blood, resulting in a more negativ e aorta-coronary sinus gradient (-9.7+/-3.1 pg/mL, P<.01). Angiotensin formation by PRA in blood during transcardiac passage increased (P<.0 01), whereas angiotensin I formed by cardiac tissues de creased dramat ically. Accordingly, in the low sodium diet, I-125-angiotensin II extr action did not change, the cardiac fractional conversion rate of I-125 -angiotensin I to I-125-angiotensin II notably decreased (P<.01), and angiotensin II formation by cardiac tissues was undetectable. The high sodium diet caused a decrease in PRA and no changes in cardiac extrac tion of radiolabeled angiotensins; conversely, angiotensin I formed by cardiac tissues, cardiac Ang I fractional conversion rate, and angiot ensin II formed during transcardiac passage significantly (P<.01 for a ll) increased. Conclusions These results provide evidence for the exis tence of a functional cardiac RAS independent of but related to the ci rculating RAS.