LOSS OF ANGIOTENSIN-II RECEPTORS IN PORTAL HYPERTENSIVE RABBITS

Decreased splanchnic vascular response to exogenous angiotensin-II (A- II) infusion in portal hypertension has recently been documented, A-II receptor density and binding affinity in the mesenteric artery, porta l vein, and adrenal gland of normal and portal hypertensive rabbits we re studied. Portal hypertension was induced by partial portal vein lig ation 3 weeks before study, There were no significant differences in s erum concentrations of sodium, potassium, A-II, serum osmolality, or h ematocrit between normal and portal hypertensive rabbits, The portal h ypertensive portal vein exhibited a 60% fall in A-II receptor number f rom 65.1 +/- 0.3 fmol/mg in normal to 27.0 +/- 8 fmol/mg (P < .05) in portal hypertension, A significant decrease in receptor number occurre d in the portal hypertensive mesenteric artery, 224 +/- 39 fmol/mg com pared with 345 +/- 45 fmol/mg in normal rabbits, and in the adrenal co rtex 6.8 +/- 1.3 pmol/mg compared with 12.1 +/- 2.5 pmol/mg in normal controls (P < .05), No significant difference in A-II. receptor affini ty was observed in tissues studied between normal and portal hypertens ive rabbits, Autoradiographic study on A-II receptors was consistent w ith data from membrane binding assays, Receptor subtype analysis showe d exclusive type I receptor binding in the mesenteric artery and porta l vein. We conclude there is a global reduction in the A-II receptor n umber in portal hypertension that may mediate much of the decreased re sponse to A-II seen in this disorder, This loss of the A-II receptor m ay partially explain hemodynamic derangements peculiar to portal hyper tension.