Changes in pulmonary vascular tone during exercise. Effects of nitric oxide (NO) synthase inhibition, L-arginine infusion, and NO inhalation.
Nitric oxide (NO) is a potent endogenous vasodilator. Its role in the normal and stressed pulmonary circulation is unclear. To better understand the importance of endogenous NO in normal physiological responses, we studied the effects of altered NO availability on the change in pulmonary vascular tone that accompanies exercise. In paired studies we measured blood flow and pressures in the pulmonary circulation at rest and during treadmill exercise at a speed of 4 mph with and without (a) N omega-nitro-L-arginine, 20 mg/kg intravenously, a selective inhibitor of NO synthase; (b) L-arginine, 200 mg/kg intravenously, substrate for NO synthase; (c) combination of the inhibitor and substrate; and (d) inhalation of NO > 30 ppm, to determine if endogenous release of NO elicits maximal vasodilation. In addition, we sought to determine the site of NO effect in the pulmonary circulation by preconstriction with either U-44619 or hypoxia (fraction of inspired O2 = 0.12) using a distal wedged pulmonary catheter technique. NO synthase inhibition raised pulmonary vascular tone equally at rest and exercise. L-Arginine reversed the effects of NO synthase inhibition but had no independent effect. NO inhalation did not reduce pulmonary vascular tone at rest or enhance the usual reduction in pulmonary vascular resistance with exercise. The effect of NO synthase inhibition was in pulmonary vessels upstream from small veins, suggesting that endogenous NO dilates primarily small arteries and veins at rest. We conclude that, in sheep, endogenous NO has a basal vasodilator function that persists during, but is not enhanced by, exercise.
Koizumi
T
T
Vanderbilt Center for Lung Research, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2650.
Gupta
R
R
Banerjee
M
M
Newman
J H
JH
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D000860:Hypoxia; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D012756:Sheep; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases