Regulation of pulmonary vascular resistance by endogenous and exogenous nitric oxide.
Inhaled nitric oxide (NO) causes selective pulmonary vasodilation under conditions of hypoxia or pulmonary vascular dysfunction. We have observed that NO affects canine pulmonary vascular resistance minimally under normal conditions. We hypothesized that endogenous NO is partly responsible for pulmonary vasomotor regulation in normoxic and hypoxic states. Dogs were studied before and after pulmonary endothelial injury with monocrotaline and N-omega-nitro-L-arginine (LNNA). Systemic vascular resistance was unaffected by NO. Under normal conditions, exogenous NO had little effect on pulmonary vascular resistance. After monocrotaline administration, baseline pulmonary vascular resistance was unchanged but decreased further in response to NO. After LNNA administration, pulmonary vascular resistance increased and there was an exaggerated increase with hypoxia that was reduced by NO. The effect of monocrotaline on in vitro endothelial function was evaluated with isolated pulmonary arteries, which showed a decreased relaxation response to bradykinin (an endothelial-dependent vasodilator) and a normal response to nitroprusside (an endothelial-independent vasodilator). These results support the hypothesis that endogenous NO is an important regulator of pulmonary vasomotor tone and is of even greater importance during hypoxia.
Van Camp
J R
JR
Department of Surgery, University of Michigan School of Medicine, Ann Arbor.
Yian
C
C
Lupinetti
F M
FM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D016686:Monocrotaline / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D019335:Nitroarginine; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014666:Vasomotor System / Q000502:physiology
D019335:Nitroarginine; D009569:Nitric Oxide; D016686:Monocrotaline; D001120:Arginine