PRORENIN, RENIN, ANGIOTENSINOGEN, AND ANGIOTENSIN-CONVERTING ENZYME IN NORMAL AND FAILING HUMAN HEARTS - EVIDENCE FOR RENIN BINDING

Background A local renin-angiotensin system in the heart is often invo ked to explain the beneficial effects of ACE inhibitors in heart failu re. The heart, however, produces little or no renin under normal condi tions, Methods and Results We compared the cardiac tissue levels of re nin-angiotensin system components in 10 potential heart donors who die d of noncardiac disorders and 10 subjects with dilated cardiomyopathy (DCM) who underwent cardiac transplantation. Cardiac levels of renin a nd prorenin in DCM patients were higher than in the donors. The cardia c and plasma levels of renin in DCM were positively correlated, and ex trapolation of the regression line to normal plasma levels yielded a t issue level close to that measured in the donor hearts. The cardiac ti ssue-to-plasma concentration (Tm) ratios for renin and prorenin were t hreefold the ratio for albumin, which indicates that the tissue levels were too high to be accounted for by admixture with blood and diffusi on into the interstitial fluid. Cell membranes from porcine cardiac ti ssue bound porcine renin with high affinity. The T/P ratio for ACE, wh ich is membrane bound, was fivefold the ratio for albumin. Cardiac ang iotensinogen was lower in DCM patients than in the donors, and its T/P ratio was half that for albumin, which is compatible with substrate c onsumption by cardiac renin. Conclusions These data in patients with h eart failure support the concept of local angiotensin production in th e heart by renin that is taken up from the circulation. Membrane bindi ng may be part of the uptake process.