Comparison of cardiopulmonary response to endogenous nitric oxide inhibition in pigs inhabited at three levels of altitude

Nitric oxide (NO) plays an important role for the pulmonary circulation in normal and chronic hypoxia. We examined effects of endogenous nitric oxide synthase (NOS) inhibition on pulmonary and systemic vascular resistance in unanesthetized pigs living at three levels of altitude to evaluate the role of NO in adaptation to a hypoxic environment. Unanesthetized male adult pigs in three areas [Matsumoto, Japan (680 m above sea level, n=5); Xing, China (2,300 m, n=5); and Maxin, China (3,750 m, n=5)] were prepared for vascular monitoring. Pulmonary (P_pa), and systemic artery pressure (P_sa) were monitored, and pulmonary artery wedge pressure (P_cwp) and cardiac output (CO) were measured before and after treatment with a non-selective NOS inhibitor, N^w-nitro-l-argine (NLA; 20 mg/kg). Pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) were (P_pa−P_cwp)/CO and P_sa/CO, respectively. Related to altitude baseline P_pa was elevated. After NLA administration, P_pa and P_sa increased and CO decreased in all animals, resulting in increases in PVR and SVR. However, there were no significant differences in the increase in PVR and SVR in the three groups of pigs. Thus, endogenous NO production contributes to regulate the basal pulmonary vascular tone, but the development of hypoxic pulmonary hypertension appears to be independent of the NO pathway in adult pigs.