Nitric oxide inhibitor altitude-dependently elevates pulmonary arterial pressure in high-altitude adapted yaks

We studied the effect of N(w)-nitro-L-arginine (NLA) on yak pulmonary vascular tone in a climatic (hypobaric/hyperbaric adjusted) chamber. Five young male yaks that had been born and reared at an altitude greater than 3800 m a.s.l. were used. After measuring control values, 20 mg/kg of NLA was administered via the jugular vein to each animal, and pulmonary hemodynamics and blood gases were repeatedly measured at simulated altitudes of 0, 2260 and 4500 m. The mean PaO2 decreased in an altitude-dependent manner, whereas there was no change in mean pulmonary arterial pressure (mPAP) or mean cardiac output (mCO). NLA significantly increased mPAP, and mean pulmonary vascular resistance (mPVR), and decreased CO at each tested altitude, and greater increases in mPAP and mPVR by NLA were observed at the higher elevations. We conclude that augmented endogenous NO production, especially at higher altitudes, accounts for the low pulmonary vascular tone observed in high-altitude adapted yaks.