ANGIOTENSIN-II RECEPTOR SUBTYPES IN BOVINE AND HUMAN VENTRICULAR MYOCARDIUM

Angiotensin II (All) binding sites in bovine and human ventricular myo cardium were characterized by a radioreceptor assay. The specific bind ing of [I-125]AII to myocardial membranes appeared to be saturable, an d it was of high affinity with apparent dissociation constants of 1.60 nM (bovine) and 1.09 nM (human). The B-max values were 39.7 fmol/mg p rotein (bovine) and 6.07 fmol/mg protein (human). Both losartan (angio tensin type 1 receptor subtype selective antagonist) and PD123177 (the angiotensin type 2 receptor subtype selective antagonist) inhibited s pecific [I-125]AII binding to bovine myocardium, and their Hill coeffi cients were less than unity. Nonlinear least-squares regression analys is has suggested the existence of two populations of [I-125]All bindin g sites that have high and low affinity for losartan or PD123177. The relative proportions of high- and low-affinity sites for losartan in b ovine myocardium were 68% and 32%, and those for PD123177 were 33% and 67%, respectively. On the other hand, specific [I-125]All binding in human myocardium was inhibited by losartan with much lower affinity an d also by PD123177 with higher affinity, compared with bovine myocardi um. The Hill coefficients for both drugs were close to one. Dithiothre itol enhanced specific [I-125]All binding to bovine myocardium in the presence of losartan, but it reduced [I-125]All binding in the presenc e of PD123177. This agent markedly enhanced specific [I-125]All bindin g to human myocardium. Thus, it is possible that bovine myocardium has both angiotensin type 1 receptor and the angiotensin type 2 receptor subtypes of All receptors whereas human myocardium has predominantly t he angiotensin type 2 receptor subtype.