Evidence for constitutive release of nitric oxide in the venous circuit of pigs.
To determine whether the venous circuit constitutively produces nitric oxide (NO), we infused the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) into anesthetized and mechanically ventilated pigs and measured venous circuit parameters. We measured cardiac output (Q) by thermodilution and obtained arterial (Part), central venous pressure (in the inferior vena cava), right atrial (Pra), pulmonary artery (PAP), and pulmonary capillary wedge pressures. A balloon was transiently inflated in the right atrium to stop venous return and obtain mean circulatory filling pressure (MCFP). Venous compliance (Cv) was measured by volume boluses. Starling curves were obtained from changes in Q with changes in Pra from the boluses. Resistance to venous return (RVR) was calculated from (MCFP - Pra)/Q. After baseline measurements, we infused 25 mg/kg of L-NAME over 10 min in seven pigs and monitored them for a further 2 h. Three others served as time controls and showed no significant hemodynamic changes. L-NAME markedly decreased cardiac output from 3.8+/-0.86 to a low of 2.0+/-0.2 L/min, and increased blood pressure from 114+/-16 to 144+/-11 mm Hg and pulmonary artery pressure from 15+/-2 to 30+/-12 mm Hg (p < 0.05). MCFP increased from 9.1+/-1.2 to 11.4+/-2.4 mm Hg (p < 0.05); Cv did not change. Cardiac function curves were markedly depressed and flattened and remained depressed for 2 h. The increase in RVR of 167% from 1.8+/-0.6 mm Hg/L/min at baseline to 5.4+/-3.7 mm Hg/L/min (p < 0.05) was similar to the 188% increase in systemic vascular resistance. These data indicate that constitutive release of NO decreases baseline venous resistance and increases capacitance. There also appears to be a worsening of cardiac function when NOS is inhibited.
Magder
S
S
Division of Critical Care, Royal Victoria Hospital, McGill University Montréal, Québec, Canada.
Kabsele
K
K
D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D013552:Swine; D014680:Veins / Q000378:metabolism*
D002245:Carbon Dioxide; D009569:Nitric Oxide; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester