Pulmonary microvascular responses to inhaled prostacyclin, nitric oxide, and their combination in anesthetized cats

Abstract

Using an X-ray television system on anesthetized cats, we directly measured internal diameter (ID) changes in identical small pulmonary vessels (100-1,100 μm ID) in response to inhalations of 25, 250, and 2,500 ng/kg/min aerosolized prostacyclin (PGI2), 4 and 34 ppm nitric oxide (NO), and the combination of aerosolized PGI2 and NO. We also compared ID changes during 250 ng/kg/min PGI2 inhalation both with and without an N(ω)-nitro-L- arginine methyl ester (L-NAME, 30 mg/kg i.v.) pretreatment. In the arteries, inhaled PGI2 increased 100-900 μm vessel ID in a dose-dependent manner but caused no significant, or only slight, ID increases in the vessels larger than this. The greatest ID increase (~22%) was in the 100-500 μm arteries in response to 2,500 ng/kg/min PGI2 inhalation. PGI2 also increased the ID of the veins (6-12%), but the results were not dose related. NO inhalation also resulted in non-uniform ID response patterns similar to PGI2 with no significant, or only minimal, ID increases of the arteries >900 μm. The simultaneous inhalation of 2,500 ng/kg/min PGI2 and 34 ppm NO increased the arterial ID (maximum ~34%) more than either drug alone and to almost the same extent as brought about by injected papaverine (2 mg/kg), a smooth muscle relaxant. Inhaled PGI2 (250 ng/kg/min) decreased pulmonary arterial pressure and increased arterial ID to nearly the same extent with or without L-NAME pretreatment. These results indicate that inhaled PGI2 and inhaled NO locally dilate 100-900 μm pulmonary arteries in a dose-dependent manner and with a similar ID response pattern, and that the combination of these drugs produces a more enhanced vasodilator effect compared to their separate effects and induces the maximum dilated states. The data also suggest that inhaled PGI2 dilates these arteries directly, rather than via secondary release of endogenous NO.