Effects of endothelin, platelet activating factor and thromboxane A2 in ferret lungs

We have compared the effects of three vasoactive agents, endothelin, platelet activating factor and thromboxane A2 analogue, U 46,619, in the pulmonary circulation of ferrets. Lungs of nine adult ferrets, body weight 1.06 +/- 0.27 kg, were isolated and perfused with sheep red blood cells suspended in Kreb's solution with 2 g% Dextran 70 (hematocrit 33 +/- 6%), under conditions of constant flow in zone 3. Endothelin-1 (ET: 0.1-1.35 micrograms/kg), platelet activating factor (PAF: 0.5-5.5 micrograms/kg) or thromboxane A2 analogue (U 46,619: 1 microgram/kg), was infused into the pulmonary artery and the pressure response determined. To locate the site of action of the agents, the pulmonary circulation was partitioned into arteries, microvessels and veins by measuring pressures in 20-50 microns diameter subpleural arterioles and venules by micropuncture, both during baseline and after the peak response to each vasoactive drug. We found that the ferret pulmonary circulation constricted in response to ET, PAF and U 46,619, but the magnitude of constriction varied. Ferret lungs were most sensitive to U 46,619 and least sensitive to PAF. The major site of action also differed among the agents; U 46,619 and ET predominantly constricted veins whereas PAF predominantly constricted arteries. We conclude that the ferret pulmonary circulation demonstrates differential responsiveness to vasoactive agents, that venous constriction is a common feature and that the predominant site of action varies with the specific agent.