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 invoked to explain the beneficial effects of ACE inhibitors in heart failure. The heart, however, produces little or no renin under normal conditions.


RESULTS
We compared the cardiac tissue levels of renin-angiotensin system components in 10 potential heart donors who died of noncardiac disorders and 10 subjects with dilated cardiomyopathy (DCM) who underwent cardiac transplantation. Cardiac levels of renin and prorenin in DCM patients were higher than in the donors. The cardiac and plasma levels of renin in DCM were positively correlated, and extrapolation of the regression line to normal plasma levels yielded a tissue level close to that measured in the donor hearts. The cardiac tissue-to-plasma concentration (T/P) ratios for renin and prorenin were threefold the ratio for albumin, which indicates that the tissue levels were too high to be accounted for by admixture with blood and diffusion into the interstitial fluid. Cell membranes from porcine cardiac tissue bound porcine renin with high affinity. The T/P ratio for ACE, which is membrane bound, was fivefold the ratio for albumin. Cardiac angiotensinogen was lower in DCM patients than in the donors, and its T/P ratio was half that for albumin, which is compatible with substrate consumption by cardiac renin.


CONCLUSIONS
These data in patients with heart failure support the concept of local angiotensin production in the heart by renin that is taken up from the circulation. Membrane binding may be part of the uptake process.
Danser
A H
AH
Department of Pharmacology, Cardiovasculair Onderzoeksinstituut Erasmus Universiteit Rotterdam, Netherlands. danser@farma.fgg.eur.nl
van Kesteren
C A
CA
Bax
W A
WA
Tavenier
M
M
Derkx
F H
FH
Saxena
P R
PR
Schalekamp
M A
MA
D000293:Adolescent; D000328:Adult; D000808:Angiotensinogen / Q000032:analysis*; D002311:Cardiomyopathy, Dilated / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004792:Enzyme Precursors / Q000032:analysis*; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry*; D007703:Peptidyl-Dipeptidase A / Q000032:analysis*; D012016:Reference Values; D012083:Renin / Q000032:analysis*
D004792:Enzyme Precursors; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A; D012083:Renin