DOWN-REGULATION OF ANGIOTENSIN-II RECEPTORS IN HYPERTROPHIED HUMAN MYOCARDIUM

1. Specific [I-125]-angiotensin II (AngII) binding in normal and hyper trophied human myocardial membranes was saturable and of high affinity , Low concentrations of unlabelled AngII and saralasin competed with [ I-125]-AngII for the binding sites in these tissues. Thus, saturable [ I-125]-AngII binding in human myocardium exhibited pharmacological spe cificity that characterized high affinity receptors for AngII. 2. Ther e was little difference in the apparent dissociation constant (K-d) va lues for [I-125]-AngII binding between normal and hypertrophied human myocardium, whereas the maximal number of binding sites (B-max) was si gnificantly (51%) lower in the hypertrophied group, Further, PD123177, a selective antagonist of the AT(2) receptor subtype, showed three or ders of magnitude higher affinity for [I-125]-AngII binding sites in b oth normal and hypertrophied myocardium than losartan, a selective ant agonist of the AT(1) receptor subtype; the Hill coefficients for these drugs were close to one. 3. A significant decrease in B-max and K-d v alues for (-)-[I-125]-iodoeyanopindolol binding between normal and hyp ertrophied human myocardium rarely occurred. 4. The present study sugg ests that both normal and hypertrophied human myocardium predominantly contains the AT(2) receptor subtype and that these receptors are down -regulated in hypertrophied tissues.