An acute increase in portal pressure or reduction in portal inflow has been shown to decrease renal plasma flow (RPF). The aim of the study was to evaluate regional and systemic hemodynamics after acute occlusion of a transjugular intrahepatic portosystemic stent-shunt (TIPSS) and study the effect of the same on plasma endothelin (ET-1) levels in the systemic circulation, renal vein, and hepatic vein. Sixteen patients attending for portography after previous TIPSS placement were studied. The shunt was acutely occluded with an angioplasty balloon for 12 minutes. Changes in portal pressure gradient (PPG), hepatic plasma flow (HPF), RPF, cardiac output (CO), and systemic vascular resistance (SVR) were measured before and after shunt occlusion. Blood was collected from the femoral artery and hepatic and renal veins for ET-1 measurement. At T = 0, SVR correlated with circulating arterial ET-1 level (r = 0.74; P <.05). After shunt occlusion (T = 12 minutes), heart rate, CO, and mean arterial pressure decreased (P <.05), whereas PPG increased (P <.05). RPF decreased from 485 +/- 55 to 282 +/- 47 mL/min (P <.01), whereas HPF increased from 700 +/- 39 to 779 +/- 33 mL/min (P <.001). There was a significant increase in arterial concentration and renal production, and decrease in hepatic production of ET-1. Veno-arterial (V-A) concentration difference in ET-1 level in the renal vein, as well as renal flux of ET-1, increased significantly, whereas hepatic vein V-A concentration difference and hepatic flux of ET-1 decreased significantly. At T = 12 minutes, ET-1 renal output correlated negatively with RPF (r = 0.72; P <.05). Results of this study show that an acute increase in portal pressure and reduction in portal inflow brought about by occlusion of a TIPSS shunt decreases RPF and increases HPF. These hemodynamic changes are accompanied by increases in arterial, renal vein, and hepatic vein ET-1 concentrations, which may possibly mediate the observed findings.