INFLUENCE OF OKY-1581 ON RESPONSES TO ARACHIDONIC-ACID IN THE FELINE PULMONARY VASCULAR BED

The effects of OKY-1581, a thromboxane synthesis inhibitor, on pulmonary vascular responses to arachidonic acid (AA) were investigated under baseline and elevated tone conditions in the intact cat chest. Under conditions of controlled blood flow at baseline tone, intralobar injections of AA increased lobar arterial pressure in a dose-related manner. These pressor responses were reduced by OKY-1581, and a small vasodilator response was unmasked. The administration of indomethacin to these same animals abolished all responses to AA. When baseline tone in the pulmonary vascular bed was elevated by infusion of U46619, intralobar injections of AA caused a biphasic change in lobar arterial pressure characterized by an initial increase followed by a secondary fall in pressure. Treatment with OKY-1581 attenuated the pressor component of the response and enhanced the depressor component of the response. All responses to AA at elevated tone were also blocked by indomethacin. Pressor responses to intralobar injections of U46619 were not altered by OKY-1581 or indomethacin and were similar under baseline and high pulmonary vascular tone conditions. The results of this study suggest that the pulmonary pressor response to AA in the cat is dependent in large part on the formation of TXA2 and also suggest that TXA2, PGI2, and vasconstrictor prostaglandins (PGF2.alpha., PGD2, PGE2) are formed from AA in the cat lung.