Down-regulation of angiotensin II receptors in hypertrophied human myocardium

1. Specific [I-125]-angiotensin II (AngII) binding in normal and hypertrophied 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 specificity that characterized high affinity receptors for AngII. 2. There was little difference in the apparent dissociation constant (K-d) values for [I-125]-AngII binding between normal and hypertrophied human myocardium, whereas the maximal number of binding sites (B-max) was significantly (51%) lower in the hypertrophied group, Further, PD123177, a selective antagonist of the AT(2) receptor subtype, showed three orders of magnitude higher affinity for [I-125]-AngII binding sites in both normal and hypertrophied myocardium than losartan, a selective antagonist 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 values for (-)-[I-125]-iodoeyanopindolol binding between normal and hypertrophied human myocardium rarely occurred. 4. The present study suggests that both normal and hypertrophied human myocardium predominantly contains the AT(2) receptor subtype and that these receptors are down-regulated in hypertrophied tissues.