Role of nitric oxide in the regulation of regional blood flow and metabolism in anaesthetized pigs.

To investigate the contribution of nitric oxide in the regulation of regional blood flow and metabolism in vivo, we administered incremental doses of N omega-L-arginine-methyl ester (L-NAME 1, 3, 10, 30 and 100 mg kg-1, intravenously) in isoflurane anaesthetized pigs. The pulmonary vascular bed exhibited a greater sensitivity to the L-NAME-induced pressor effects compared with the systemic arterial bed as the slope of the dose-response curve was steeper (42.9 +/- 4.3 vs. 24.3 +/- 3.6, P < 0.05) and the dose of L-NAME required to induce a 25% pressure increase was lower (PD25 of 6.2 +/- 2.5 vs. 22.8 +/- 5.2 mg kg-1, P < 0.05). L-NAME infusion produced a dose-dependent reduction in cardiac output that was evenly distributed among the mesenteric, femoral, hepatic and carotid arterial circulation as demonstrated by unchanged regional blood flows-to-cardiac output ratios, except in the kidney where the L-NAME-induced vasoconstriction was most pronounced (renal blood flow/cardiac output decreased from 6.2 +/- 0.6 to 3.7 +/- 0.7% after 100 mg kg-1 of L-NAME, P < 0.05). After the administration of L-NAME 30 mg kg-1, intestinal O2 uptake (Vo2) increased (+39 +/- 3%, P < 0.05) whereas renal Vo2 tended to decrease (-19 +/- 4%, P = 0.07) and whole body Vo2 remained unchanged. Plasma noradrenaline and adrenaline concentrations did not change significantly with L-NAME infusion. These data demonstrate that in anaesthetized pigs, endogenous nitric oxide is most important for the regulation of pulmonary and renal blood flows and in spite of unchanged global metabolic demand, nitric oxide inhibition leads to an increase in intestinal Vo2 associated with enhanced gut motility without rise in circulating lactate levels.