Effect of inhaled nitric oxide in endothelin-1-induced pulmonary hypertension

The interaction of two vasoactive substances, the vasoidilator nitric oxide (NO) and the complex-acting peptide endothelin-1 (ET-1), may help explain the pathophysiology of pulmonary hypertension, an important part of many pulmonary disorders in neonates. To understand better the interactions of inhaled NO and ET-1, we investigated the effects of ET-1 infusions with and without inhaled NO in two groups of piglets, one group pretreated with L-nitro-arginine methylester (L-NAME) and the other not pretreated. Inhaled NO (60 ppm) was administered during infusion of 1.0 microgram/kg or 2.5 micrograms/kg of ET-1. In animals not pretreated with L-NAME, the increase in PVR and in SVR induced by either dose of ET-1 was not reduced with administration of NO. The increase in systemic vascular resistance with ET-1 was greater (mean increase of 50% above baseline with 1.0 microgram/kg ET-1 and 100% with 2.5 micrograms/kg ET-1 by 5 min) than the increase in PVR, but the PVR/SVR ratio did not change during ET-1 administration. In contrast, animals pretreated with L-NAME did demonstrate inhibition of ET-1-induced increase in PVR with NO. No differences in effects on SVR were noted. We conclude that ET-1-induced increases in PVR are not diminished by 60 ppm of inhaled NO unless there has been inhibition of endogenous NO production.