Selective pulmonary vasodilation by inhaled nitric oxide is due to hemoglobin inactivation.
BACKGROUND
Inhaled nitric oxide gas selectively decreases pulmonary artery pressure without affecting systemic arterial pressure. To determine if the selective pulmonary vasodilating effect of inhaled nitric oxide gas is due to inactivation by hemoglobin, we studied the ability of whole blood to inhibit the vasodilator activity of effluent from isolated lungs exposed to inhaled nitric oxide.


RESULTS
The effluent from ventilated, Krebs-perfused rabbit lungs was passed directly over 3- to 4-mm rabbit aortic rings. Inhaled nitric oxide (150 ppm for 3 minutes) reduced pulmonary perfusion pressure, elevated by a continuous infusion of U46619, by 35 +/- 7% (mean +/- SEM, n = 5). Lung effluent from this series of experiments caused 40 +/- 13% relaxation of phenylephrine-preconstricted aortic rings. When blood was added to the combined lung/ring perfusion cascade (final hemoglobin concentration, 1 g/dL), inhaled nitric oxide again significantly reduced pulmonary perfusion pressure, but the effluent now failed to relax the aortic rings (30 +/- 6% [control] versus 1.5 +/- 1% [blood]). Both reduction in pulmonary perfusion pressure and relaxation of the rings during nitric oxide exposure were unchanged from control values after discontinuing the blood infusion.


CONCLUSIONS
The presence of hemoglobin, even in extremely small amounts, restricts the vasodilating effect of inhaled nitric oxide gas to the pulmonary circulation.
Rimar
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Department of Anesthesiology, Yale University School of Medicine, New Haven, Conn. 06510.
Gillis
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CN
D000280:Administration, Inhalation; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001769:Blood / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D006454:Hemoglobins; D009569:Nitric Oxide