Angiotensin II increases portosystemic collateral resistance in portal hypertension.
The decreased vasoconstrictive response of the splanchnic vasculature in portal hypertension (PHT) to angiotensin II (ANGII) is newly established. This could explain the limited ability of PHT patients to compensate in hypovolemic shock. However, the effect of ANGII upon portosystemic collateral resistance (Rc) is not known. We hypothesized that ANGII could directly effect Rc and thus change portal venous pressure (PVP). Chronic PHT was induced in New Zealand white rabbits by partial portal vein ligation 3 weeks prior to study. Splanchnic blood flow and portosystemic shunt (PSS) were measured simultaneously in six normal rabbits and then in six PHT rabbits at baseline and during intravenous ANGII infusion at 1.0 microgram/kg/min. Flow and resistance were standardized to 100 g small intestine weight. Superior mesenteric artery flow (Qsma) in normal rabbits was 64.9 +/- 3.6 ml/min, increased to 134.6 +/- 13.5 ml/min in the PHT animals (P less than 0.001) and was reduced 30% (P less than 0.05 vs PHT baseline) with ANGII. Concomitantly, PVP in the PHT animals was twice normal, 7.0 +/- 0.32 vs 14.4 +/- 0.55 mm Hg (P less than 0.001) and rose slightly with ANGII. The high PSS in PHT (84 +/- 6.0%, P less than 0.001 vs normal) was not affected significantly by ANGII infusion. Rc in the PHT rabbits rose 50% from 0.06 +/- 0.001 to 0.09 +/- 0.01 mm Hg/ml/min (P less than 0.001) with ANGII. This is the first evidence for a vasoconstrictive response in portosystemic collaterals during ANGII infusion. This change in collateral resistance causes both PVP and PSS to remain pathologically elevated in PHT despite a fall in portal inflow, thus predisposing to repeat variceal bleeding.
Campbell
K A
KA
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Wu
Y P
YP
Sitzmann
J V
JV
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects*; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D011168:Portal System / Q000187:drug effects*; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects*; D014690:Venous Pressure / Q000187:drug effects
D000804:Angiotensin II