Comparison of pulmonary vascular response to endogenous nitric oxide inhibition in sheep and pigs living at 2,300 m.
To compare the role of nitric oxide in an adaptive process to chronic hypoxia, we examined the effects of endogenous nitric oxide synthase inhibition on pulmonary vascular tone in conscious sheep and pigs living at high altitude. Unanesthetized male sheep (n = 6) and pigs (n = 5), born and residing in the highlands of Qinghai Province, China (2,300-3,000 m a.s.l.) were studied at that altitude. Pulmonary artery pressure (P(pa)), pulmonary artery wedge pressure (P(cwp)), and cardiac output (CO) were measured. Pulmonary vascular resistance (PVR) was calculated as (P(pa)- P(cwp))/ CO. Using a climatic chamber, hemodynamic measurements during exposures to atmospheric pressures corresponding to altitudes of 0, 2,300, and 4,500 m a.s.l. were performed with and without NO inhibition, using N(w)-nitro- L-argine (NLA; 20 mg kg(-1)), a potent stereospecific competitive inhibitor of nitric oxide synthase. P(pa) and PVR at baseline (2,300 m) and during hypoxic exposure (4,500 m) were significantly higher in pigs than in sheep. After NLA administration, P(pa) increased and CO decreased in both animals, resulting in significantly increased PVR at baseline and during hypoxic exposure. However, there were no significant differences in the percent increase in basal or hypoxic PVR after NLA administration between sheep and pigs. We conclude that augmented endogenous NO production could contribute to the regulation of pulmonary vascular tone at high altitude in sheep and pigs. However, it is unlikely that NO is responsible for the different pulmonary vascular tones between sheep and pigs at basal condition at moderately high altitude.
First Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, 390-8621, Nagano, Matsumoto, Japan.
Zonghai
Z
Ruan
Tomonobu
T
Koizumi
Akio
A
Sakai
Takeshi
T
Ishizaki
Zhangang
Z
Wang
Qiuhong
Q
Chen
Xiaoqin
X
Wang
D000531:Altitude; D000818:Animals; D001784:Blood Gas Analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep / Q000097:blood / Q000502:physiology*; D013552:Swine / Q000097:blood / Q000502:physiology*
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide