Influence of prostaglandin synthesis inhibitors on pulmonary vasodilatory effects of hydralazine in dogs with hypoxic pulmonary vasoconstriction.
TO DETERMINE WHETHER HYDRALAZINE, A SYSTEMIC VASODILATOR, EXERTED A SIMILAR EFFECT ON THE PULMONARY CIRCULATION, WE STUDIED THE CIRCULATORY CHANGES IN DOGS DURING THREE INTERVENTIONS: (a) the control state during room air ventilation; (b) during continuous hypoxic ventilation with 10% oxygen, and maintaining continuous hypoxic ventilation; and (c) after 1 mg/kg hydralazine intravenously. Ventilation with 10% oxygen caused the mean pulmonary artery pressure to increase from 10+/-1.2 to 23+/-2.4 mm Hg (P < 0.01) and the pulmonary arteriolar resistance to increase from 1.51+/-0.19 to 5.87+/-1.10 U (P < 0.01). Hydralazine significantly lowered the pulmonary artery pressure (23.0+/-2.4 to 14.3+/-1.5 mm Hg, P < 0.01) and the pulmonary arteriolar resistance (5.87+/-1.10 to 2.87+/-0.52 U, P < 0.01). Femoral artery pressure, pulmonary artery wedge pressure, heart rate, and cardiac output remained unchanged throughout. To ascertain the contribution of the prostaglandin system to the pulmonary vasodilator effects of hydralazine, we pretreated a group of dogs with the prostaglandin synthetase inhibitor, indomethacin, 5 mg/kg s.c., twice daily for 2 d. These animals then underwent identical studies.The pretreated dogs had comparable base-line and hypoxia hemodynamic data. However, hydralazine had no effect on pulmonary artery pressure (23.3+/-1.6 vs. 21.7+/-2.3 mm Hg, NS) or pulmonary arteriolar resistance (8.03+/-1.09 vs. 7.14+/-1.42, NS) during continuous hypoxic ventilation in the indomethacin-pretreated group. Pretreatment with indomethacin did not, however, block the pulmonary vasodilator effects of intravenous prostacyclin (PGI(2)). Pretreatment with meclofenamate, a cyclo-oxygenase inhibitor structurally unrelated to indomethacin, also blocked the effects of hydralazine during hypoxic ventilation. These data suggest that hydralazine exerts a pulmonary vasodilatory effect during hypoxia-induced pulmonary vasoconstriction, and that this vasodilator effect may be mediated by prostaglandins.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006830:Hydralazine / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D010100:Oxygen / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects*; D012119:Respiration; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D011453:Prostaglandins; D062367:ortho-Aminobenzoates; D006830:Hydralazine; D008469:Meclofenamic Acid; D010100:Oxygen; D007213:Indomethacin