Endothelium-dependent relaxation and the acute pulmonary vascular response to alveolar hyperoxia in neonatal pigs.
To determine whether hyperoxia increases the production of endothelium-derived relaxing factor, we studied the effect of oxygen on pulmonary vascular ring tension and regional lung perfusion. In vitro, hyperoxia stimulated endothelium-independent constriction of neonatal porcine pulmonary arterial rings. In vessels with intact endothelium, hyperoxia stimulated a concomitant increase in the production of endothelium-derived relaxing factor. In sedated neonatal pigs, colored microspheres were used to evaluate relative lung perfusion when two lung regions were independently ventilated with room air, and subsequently, when one lung region was ventilated with 100% oxygen. The proportion of flow to the hyperoxic lung region was not significantly increased until the production of endothelium-derived relaxing factor was inhibited by NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester. Thus, hyperoxia stimulated opposing effects on the tension of isolated vascular rings. One mechanism of oxygen-mediated relaxation results from an increase in the production of endothelium-derived relaxing factor. However, in vivo, alveolar hyperoxia may stimulate an acute pulmonary vasodilatory response which is not mediated by endothelium-derived relaxing factor.
Day
R W
RW
Department of Pediatrics, University of California, Los Angeles School of Medicine.
Klitzner
T S
TS
Ignarro
L J
LJ
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002245:Carbon Dioxide / Q000097:blood; D046508:Culture Techniques; D006863:Hydrogen-Ion Concentration; D008168:Lung / Q000098:blood supply*; D008297:Male; D008863:Microspheres; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D019335:Nitroarginine; D010100:Oxygen / Q000097:blood / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine
D002245:Carbon Dioxide; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester