Prostacyclin aerosol and inhaled nitric oxide fail to reverse pulmonary vasoconstriction induced by thromboxane analogue in dogs

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Abstract
Inhalation of either prostacyclin (PGI2) as an aerosol or nitric oxide (NO) has been shown to elicit selective pulmonary vasodilation during hypoxic pulmonary vasoconstriction in dogs. Hypoxia may produce cardiovascular changes confounding interpretation of drug effects. Therefore, we investigated the effects of PGI2‐aerosol and inhaled NO (50 p.p.m.) on pulmonary pressure‐flow relationships (P/Q_plots) during thromboxane analogue (U46619) induced pulmonary vasoconstriction.In eight anaesthetized dogs infusion of U46619 (0.33 ± 0.18 μg kg_1min‐1) increased the slope (3.5 ± 1.1 to 8.4 ± 1.7 mmHg L‐1min‐1,P <0.001) and the intercept (4.4±2.3 to 10.2 ± 4.6 mmHg,P <0.01) ofP/Qplots indicating pulmonary vasoconstriction. Inhalation of both aerosolized PGI2solution (10μgmL‐1) and NO (50 p.p.m.) reduced neither the slope nor the intercept of theP/Q_plots. Increasing the concentration of the aerosolized PGI2solution to 50 μg mL‐1:(n= 3) did not enhance the effect on pulmonary circulation but systemic vascular resistance fell by 23%. Oxygenation and intrapulmonary shunt remained unchanged during both PGI2‐aerosol and inhaled NO. The failure of PGI2‐aerosol to induce pulmonary vasodilation indicates that during aerosolization PGI2‐concentrations at receptor sites on pulmonary vessels were insufficient to surmount U46619 induced vasoconstriction; this notion is supported by unchanged arterial plasma concentrations of the PGI2degradation product 6‐keto‐PGFlα. Considering that NO inhaled at comparable concentrations in sheep reversed U46619 induced pulmonary vasoconstriction, species differences may account for the failure of both PGI2‐aerosol and NO to dilate pulmonary vessels in dogs.