Prostacyclin aerosol and inhaled nitric oxide fail to reverse pulmonary vasoconstriction induced by thromboxane analogue in dogs.
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 micrograms kg-1 min-1) increased the slope (3.5 +/- 1.1 to 8.4 +/- 1.7 mmHg L-1 min-1, P < 0.001) and the intercept (4.4 +/- 2.3 to 10.2 +/- 4.6 mmHg, P < 0.01) of P/Q plots indicating pulmonary vasoconstriction. Inhalation of both aerosolized PGI2 solution (10 micrograms mL-1) and NO (50 p.p.m.) reduced neither the slope nor the intercept of the P/Q plots. Increasing the concentration of the aerosolized PGI2 solution to 50 micrograms 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 PGI2 degradation product 6-keto-PGF1 alpha. 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.
Welte
M
M
Department of Anaesthesiology, University of Munich, Germany.
Zwissler
B
B
Habler
O
O
Kleen
M
M
Messmer
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D015656:Respiratory Mechanics / Q000187:drug effects; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000336:Aerosols; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol