Inhaled nitric oxide (NO) and inhaled prostacyclin (PGI₂) produce selective reductions in pulmonary vascular resistance (PVR) through differing mechanisms. NO decreases PVR via cGMP, and PGI₂ produces pulmonary vasodilation via cAMP. As a general pharmacological principle, two drugs that produce similar effects via different mechanisms should have additive or synergistic effects when combined. We designed this study to investigate whether combined inhaled NO and PGI₂ therapy results in additive effects during chronic pulmonary hypertension in the rat. Monocrotaline injected 4 wk before study produced pulmonary hypertension in all animals. Inhaled NO (20 parts/million) reversibly and selectively decreased pulmonary artery pressure (Ppa) with a mean reduction of 18%. Four concentrations of PGI₂ were administered via inhalation (5, 10, 20, and 80 µg/ml), both alone and combined with inhaled NO. Inhaled PGI₂ alone decreased Ppa in a dose-dependent manner with no change in mean systemic arterial pressure. Combined inhaled NO and PGI₂ selectively and significantly decreased Ppa more did than either drug alone. The effects were additive at the lower concentrations of PGI₂ (5, 10, and 20 µg/ml). The combination of inhaled NO and inhaled PGI₂ may be useful in the management of pulmonary hypertension.

pulmonary vascular resistance; monocrotaline; adenosine 3',5' cyclic monophosphate; guanosine 3',5' cyclic monophosphate; rat; vasodilator

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