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, portal vein, and adrenal gland of normal and portal hypertensive rabbits were studied. Portal hypertension was induced by partial portal vein ligation 3 weeks before study. There were no significant differences in serum concentrations of sodium, potassium, A-II, serum osmolality, or hematocrit between normal and portal hypertensive rabbits. The portal hypertensive portal vein exhibited a 60% fall in A-II receptor number from 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 occurred in the portal hypertensive mesenteric artery, 224 +/- 39 fmol/mg compared with 345 +/- 45 fmol/mg in normal rabbits, and in the adrenal cortex 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 affinity was observed in tissues studied between normal and portal hypertensive rabbits. Autoradiographic study on A-II receptors was consistent with data from membrane binding assays. Receptor subtype analysis showed exclusive type I receptor binding in the mesenteric artery and portal vein. We conclude there is a global reduction in the A-II receptor number in portal hypertension that may mediate much of the decreased response to A-II seen in this disorder. This loss of the A-II receptor may partially explain hemodynamic derangements peculiar to portal hypertension.
Sitzmann
J V
JV
Department of Surgery, Johns Hopkins Medical Institution, Baltimore, MD, USA.
Wu
Y
Y
Aguilera
G
G
Cahill
P A
PA
Burns
R C
RC
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D001713:Biphenyl Compounds / Q000494:pharmacology; D006975:Hypertension, Portal / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008026:Ligation; D019808:Losartan; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D011169:Portal Vein / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D019808:Losartan