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

Using an X-ray television system on anesthetized cats, we directly measured internal diameter (ID) changes in identical small pulmonary vessels (100-1 ,100 mu m ID) in response to inhalations of 25, 250, and 2,500ng/kg/min aer osolized prostacyclin (PGI(2)), 4 and 34 ppm nitric oxide (NO), and the com bination of aerosolized PGI(2) and NO. We also compared ID changes during 2 50ng/kg/min PGI(2) inhalation both with and without an N-omega-nitro-L-argi nine methyl ester (L-NAME, 30mg/kg I.V.) pretreatment. In the arteries, inh aled PGI(2) increased 100-900 mu m 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 (similar to 22%) was in the 100-500 mu m arteries in response to 2,500 ng/kg/min PGI(2) inhalation. PGI(2) also in creased 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 PGI(2) with no significant, or only minimal, ID increases of the arteries > 900 mu m. The simultaneous inhalation of 2,500 ng/kg/min PGI(2) and 34 pp m NO increased the arterial ID (maximum similar to 34%) more than either dr ug alone and to almost the same extent as brought about by injected papaver ine (2 mg/kg), a smooth muscle relaxant. Inhaled PGI(2) (250 ng/kg/min) dec reased pulmonary arterial pressure and increased arterial ID to nearly the same extent with or without L-NAME pretreatment. These results indicate tha t inhaled PGI(2) and inhaled NO locally dilate 100-900 mu m pulmonary arter ies in a dose-dependent manner and with a similar ID response pattern, and that the combination of these drugs produces a more enhanced vasodilator ef fect compared to their separate effects and induces the maximum dilated sta tes. The data also suggest that inhaled PGI(2) dilates these arteries direc tly, rather than via secondary release of endogenous NO.