Studies on the mechanism of an antibiotic ionophore, R02-2985 (X537A) in the conscious chronically instrumented dog: involvement of the prostaglandin synthetic pathway.

Conscious dogs were pretreated with a large dose of indomethacin in order to test the hypothesis that prostaglandin synthesis may be involved in the mechanism of action of the inophore R02-2985. The increase in renal blood flow and decrease in renal vascular resistance usually produced by R02-2985 were inhibited by indomethacin. In fact, the calculated renal resistance doubled. In contrast to the effects on renal circulation, indomethacin did not affect coronary blood flow increases which occur independent of contractility changes produced by this ionophore. Effects associated with facilitated release of catecholamines, ie, increases in heart rate, central aortic pressure, and dP/dt were prolonged in comparison to the control study published earlier where these parameters returned to control levels within 2.5 h, thus suggesting that prostaglandin synthesis may somehow potentiate the effects of R02-2985 on the release of catecholamines in vivo.