THE EFFECTS OF EICOSANOID SYNTHESIS INHIBITORS ON NORMOXIC AND HYPOXIC PULMONARY VASCULAR TONE IN DOGS

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Abstract
Prostaglandins [PG] have been implicated as possible modulators of normoxic and hypoxic pulmonary tone partly because of studies using cycloxygenasae inhibitors, but these drugs may exert effects that are indendent of PG cyclooxygenase. The hemodyamic effects of the acute i.v. administration of 3 cylooxygen inhibitor drug in doses that inhibit PG synthesis were studied in intact anesthetized dogs: indomethacin 5 mg/kg, meclofenamate 5 mg/kg and ibuprofen 12.5 mg/kg. During room air ventilation, the administration of indomethacin produced an increase in mean pulmonary arterial pressure (8.0 .+-. 1.27 to 13.1 .+-. 1.52 mm Hg, P < 0.01) and pulmonary vascular resistance (1.2 .+-. 0.23 to 2.7 .+-. 0.39, P < 0.01), whereas meclofenamate and ibuprofen had no effect. Indomethacin given during hypoxic ventilation slightly but insignificantly increased pulmonary artery pressure and pulmonary vascular resistance when compared with hypoxia alone and with the administration of vehicle or meclofenamate. Treatment with indomethacin or meclofenamate 5 mg/kg given s.c. twice daily for 2 days had no effect on normoxic or hypoxic pulmonary tone. The combined cyclooxygenase-lipoxygenase inhibitor BW 755C [3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrozoline]. In doses of 25 mg/kg given i.v. did not inhibit hypoxic pulmonary vasconstriction. PG do not appear to play a major physiologic role in modulating normoxic or hypoxic pulmonary vasomotor tone in intact anesthetized dogs and the indomethacin-induced increases in pressure and resistance are independent of inhibition of PG cyclooxygenase.