Combined inhaled nitric oxide and inhaled prostacyclin during experimentalchronic pulmonary hypertension

Inhaled nitric oxide (NO) and inhaled prostacyclin (PGI(2)) produce selecti ve reductions in pulmonary vascular resistance (PVR) through differing mech anisms. NO decreases PVR via cGMP, and PGI(2) produces pulmonary vasodilati on via cAMP. As a general pharmacological principle, two drugs that produce similar effects via different mechanisms should have additive or synergist ic effects when combined. We designed this study to investigate whether com bined inhaled NO and PGI(2) therapy results in additive effects during chro nic pulmonary hypertension in the rat. Monocrotaline injected 4 wk before s tudy produced pulmonary hypertension in all animals. Inhaled NO (20 parts/m illion) reversibly and selectively decreased pulmonary artery pressure (Ppa ) with a mean reduction of 18%. Four concentrations of PGI(2) were administ ered via inhalation (5, 10, 20, and 80 mu g/ml), both alone and combined wi th inhaled NO. Inhaled PGI(2) alone decreased Ppa in a dose-dependent manne r with no change in mean systemic arterial pressure. Combined inhaled NO an d PGI(2) selectively and significantly decreased Ppa more did than either d rug alone. The effects were additive at the lower concentrations of PGI(2) (5, 10, and 20 mu g/ml). The combination of inhaled NO and inhaled PGI(2) m ay be useful in the management of pulmonary hypertension.