Effects of endothelin in portal hypertensive rats.

1. Effects of endothelin-1 on systemic arterial blood pressure, heart rate and portal venous pressure were compared in normal Sprague-Dawley rats and rats with portal hypertension induced by CCl4 and partial portal vein ligation. 2. Endothelin-1 produced biphasic effects on systemic blood pressure and portal venous pressure in all three groups of rats. However, the magnitude of the changes in blood pressure was less in portal hypertensive rats. 3. The ability of endothelin-1 to increase the portal venous pressure was also significantly diminished in portal hypertensive rats. On the other hand, the initial decrease in portal pressure was augmented in rats with partial portal vein ligation, and disappeared at higher dosage in CCl4-treated rats. 4. In accordance with the pressure recording in vivo, the dose-response vasoconstrictive activity of endothelin-1 was significantly attenuated in the intrahepatic vasculature. 5. The plasma immunoreactive endothelin concentration was significantly higher (5.55 +/- 0.81 fmol/ml) in Sprague-Dawley rats than in CCl4-treated rats (2.83 +/- 0.56 fmol/ml) and rats with partial portal vein ligation (2.68 +/- 0.53 fmol/ml). 6. It was concluded that a lower plasma level of endothelin and a reduced vascular responsiveness may contribute, at least in part, to the hyperdynamics of portal hypertension.