title: Sites of inhaled NO-induced vasodilation during hypoxia and U-46619 infusion in isolated lamb lungs.
abstract: The sites of relaxation in response to inhaled nitric oxide (NO) were investigated using the vascular occlusion technique in isolated blood-perfused lungs from 1- to 3-mo-old lambs. In one group of 10 lungs, inhaled NO (45 ppm) was administered during hypoxia- and U-46619-induced pulmonary vasoconstriction. In a second group of 5 lungs, responses to inhaled NO and infused sodium nitroprusside (SNP, 3 micrograms.kg-1.min-1) during U-46619-induced hypertension were compared. Hypoxia caused significant pulmonary vasoconstriction, with increases in the pressure gradients of large and small arteries and small veins, as defined by vascular occlusion. Inhaled NO significantly reduced the total pulmonary pressure gradient by 67% and relaxed both large and small arteries. Infusion of U-46619 caused significant increases in all segmental pressure gradients. While inhaled NO was effective in relaxing the large and small arteries and the small veins, it had no effect on the large veins. Infusions of SNP, a nitrosovasodilator thought to act like endogenous NO, caused a similar degree of total relaxation as NO (81 vs. 77%, respectively). However, in contrast to inhaled NO, SNP was effective in reducing the pressure gradient of the large pulmonary veins. These results suggest that rapid binding to and thus inactivation of inhaled NO by hemoglobin limit its efficacy as a pulmonary venous dilator.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Tod
authors.forename: D C
authors.initials: DC
authors.lastname: O'Donnel
authors.forename: J B
authors.initials: JB
authors.lastname: Gordon
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002950:Citrate (si)-Synthase; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014662:Vasoconstrictor Agents; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents
chemical_list: D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D013928:Thromboxane A2; D002950:Citrate (si)-Synthase