Evidence for renal glomerular receptors for angiotensin II

Abstract

Monoiodinated angiotensin II (2000 mCi/μmole) was found to bind specifically to isolated rat glomeruli. Equilibrium was reached after 12 min and specific binding represented more than 95% of total binding. Dissociation after addition of an excess of unlabelled molecules was rapid. The k(1) and k(-1) association and dissociation constants determined from time course studies were 0.254 ± 0.078 x 1010 M-1 min-1 and 0.102 ± 0.018 min-1, min-1, respectively and the ratio k(-1)/k(1) (K[D]) was 4.51 ± 0.55 x 10-11 M. Angiotensin II, liberated from glomerular binding sites at low pH, retained the ability to bind to fresh membranes. Angiotensin II, angiotensin I, ileu8 angiotensin II and sarc1 ileu8 angiotensin II were all equally effective as competitive inhibitors of 125I angiotensin binding. In a preparation of isolated rat glomeruli, mean glomerular diameter decreased as a function of 125I angiotensin II concentration according to a sigmoidal effect vs. log dose curve and the calculated K[D] (6 x 10-11 M) was similar to that obtained from binding studies. Specific binding of angiotensin II at physiological plasma concentration to rat glomeruli and correlation of this binding with glomerular vasoreactivity suggest a physiological role for this hormone in regulation of glomerular filtration.