Endogenous nitric oxide and pulmonary circulation response to hypoxia in high-altitude adapted Tibetan sheep.

Nitric oxide (NO) is important for the pulmonary circulation response to acute and chronic hypoxia. We examined effects of endogenous nitric oxide synthase (NOS) inhibition on pulmonary vascular tone in response to hypoxia in Tibetan sheep dwelling at 3,000 m above sea level using a pressure chamber. Unanaesthetized male sheep living at 2,300 m above sea level ( n=7) were prepared for vascular monitoring. Pulmonary artery ( P(pa)), pulmonary artery wedge ( P(cwp)) and systemic artery pressures together with cardiac output (CO) were measured, and pulmonary vascular resistance (PVR) was calculated as ( P(pa)- P(cwp))/CO. A non-selective NOS inhibitor, N(omega)-nitro- l-arginine (NLA; 20 mg kg(-1)), and a selective NOS inhibitor, ONO-1714 (0.1 mg kg(-1)), were used and measurements were made at 0 m, 2,300 m, and 4,500 m, with and without the NOS inhibitors. After NLA, P(pa) increased slightly and CO decreased in animals at baseline (2,300 m). The increased PVR after NLA at 4,500 m was greater than that at 2,300 m ( P<0.05). Selective NOS inhibition increased PVR at baseline, but not at 4,500 m. The enhanced pulmonary vasoconstriction after NO inhibition at basal and hypoxic conditions suggests a modulating role of NOS bioactivity in the pulmonary circulation and that augmented endothelial NOS plays a counterregulatory role in the pulmonary vasoconstrictor response to acute hypoxia in high-altitude adapted Tibetan sheep.