Angiotensin II blockade in existing hypovolemia: Effects of candesartan inthe porcine splanchnic and renal circulation

Angiotensin II (AngII) is an important vasoconstrictor during hypovolemia. This study focused on the effects of the AngII receptor blocker candesartan on intestinal, hepatic, and renal hemodynamics during severe hypovolemia w hen administered in preexisting moderate hypovolemia, It was hypothesized t hat specific AngII receptor blockade might enhance splanchnic perfusion dur ing hypovolemia. Fasted, anesthetized, ventilated, juvenile pigs were hemor rhaged by 20% of the blood volume for 30 min. Animals were then randomized to receive candesartan (CAND, n = 11) or the vehicle (CTRL, n = 10) prior t o further hemorrhage to 40% of the blood volume for 30 min. The shed blood was then retransfused. Systemic and splanchnic hemodynamics were recorded i ncluding intestinal mucosal, superficial and parenchymal hepatic, and corti cal and medullary renal microcirculation by laser-Doppler flowmetry. Arteri al blood gases were analysed. Candesartan-treated animals maintained mesent eric and jejunal mucosal perfusion during 40% hypovolemia compared to CTRL animals, while no differences were observed in the hepatic and renal circul ation. Retransfusion restored mesenteric and renal blood flows despite pers istent hypotension and reduced cardiac output in both CAND and CTRL animals . Renal medullary and hepatic parenchymal microcirculation failed to recove r during retransfusion in both CAND and CTRL animals. Arterial acidosis, hy percarbia, and a negative base excess were observed in CTRL animals followi ng retransfusion whereas those parameters were normalised in CAND animals. Administration of candesartan in moderate hypovolemia ameliorated the reduc tion and consequences of mesenteric and intestinal, but not hepatic perfusi on during severe hypovolemia. No adverse effects were observed in the renal circulation.