Ischemia reperfusion induces an increase in the hepatic portal vasoconstrictive response to endothelin-1

Microvascular impairment observed during reperfusion following ischemia (IR ) is a major determinant of the development of liver injury. Previous studi es have shown that hyper-responsiveness to endothelin-1 (ET-1) contributes to microvascular dysfunction following a primarily inflammatory stress indu ced by endotoxin, The present study investigates whether a similar hypercon tractile response to ET-1 occurs in the hepatic portal system of IR rats. P entobarbital-anesthetized Sprague-Dawley rats underwent liver ischemia of t he left and medial lobes for 60 min (IR, n = 8) or a sham operation (n = 8) , Six hours after reperfusion, the liver was isolated and perfused through the portal vein, Baseline portal pressure (P-p), portal flow (Q(p)), and si nusoidal diameter (D-s) were measured before and 3 and 10 min after adding ET-1 (1 nM). In baseline, IR livers had a significantly greater P-p, portal resistance, and D-s than sham. ET-1 significantly increased P-p and portal resistance and significantly decreased Q(p) and D-s in IR and sham rats. H owever, these effects were significantly greater in IR. The results of the present study demonstrate that IR increases the porto-hepatic contractile r esponse to ET-1, which may further sensitize the portal circulation to elev ated ET-1 and may be a prominent contributor to the development of microvas cular impairment following IR.