CARDIOVASCULAR ACTIONS OF NITRIC OXIDE SYNTHASE INHIBITION IN THE PORTAL HYPERTENSIVE RAT

Summary 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 shamoperated 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 shamoperated 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.