Cardiovascular actions of nitric oxide synthase inhibition in the portal hypertensive rat.

Abstract

We have investigated the actions of the nitric oxide synthase inhibitor L-NMMA in the portal hypertensive Wistar rat in vivo. Resting blood pressure in the anaesthetised portal hypertensive rat was 107.8+/-11.0 / 79.2+/-11.7 mmHg (n = 12), which was significantly lower than in sham-operated animals (143.0+/-3.8 / 114.0+/-4.0 mmHg, n = 19; P < 0.01). Cardiac output was significantly higher in portal hypertensive (30.2+/-1.0 ml min(-1) per 100 g, n = 12) than sham-operated animals (23.7+/-2.2 ml min(-1) per 100 g, n = 13; P < 0.01). Intravenous injection of L-NMMA (10 mg kg(-1)) significantly increased systemic blood pressure in both portal hypertensive and sham-operated animals to 123.0+/-15.0 / 93.4+/-14.0 mmHg and 162.1+/-5.7 / 131.6+/-6.0 mmHg, respectively. The magnitude of the changes were similar in both groups. This increase in blood pressure was accompanied by a decrease in cardiac output to 88.5+/-2.8% and 91.5+/-2.4% of control in portal hypertensive and sham-operated animals, respectively (no significant difference). L-NMMA (10 mg kg(-1)) had similar effects on small mesenteric arterial conductance in both portal hypertensive and sham operated animals, reducing conductance to 84.4+/-3.6% (n = 6) and 82.7+/-1.2% (n = 4) of control, respectively. It is concluded that L-NMMA has similar effects in vivo in portal hypertensive as compared with sham-operated rats. Hence, an enhancement of endothelium-derived nitric oxide is not involved in the hyperdynamic state following portal hypertension in the rat.