PLATELET-ACTIVATING-FACTOR CAUSES PULMONARY VASODILATION IN THE RAT

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Abstract
Although platelet-activating factor (PAF) has generally been found to be a pulmonary pressor substance, its vasoactivity has not been measured at low doses in a preconstricted pulmonary vascular bed. Thus, we examined the effects of low concentrations of PAF on systemic and pulmonary hemodynamics during normoxia and acute hypoxia in conscious, catheterized rats (weighing 250 to 350 g), on hypoxic vasoconstriction in isolated rat lungs, and on norepinephrine-induced constriction in isolated, intact, and endothelium-denuded rat pulmonary arteries. In normoxic rats, injections of 0.001, 0.01, and 1.0 .mu.g PAF/rat given intravenously caused progressively greater, transient systemic hypotension and tachycardia. The 2 higher doses also decreased cardiac output and pulmonary arterial pressure (Ppa). In 5 rats breathing 8% O2, Ppa fell from 36 .+-. 2 to 30 .+-. 2 torr within 1 min of injection of 0.01 .mu.g PAF and did not change (39 .+-. 2 versus 40 .+-. 2 torr) 1 min after 0.25% albumin (vehicle). Total pulmonary resistance was 0.18 .+-. 0.04 torr/ml/min in normoxic rats and 0.19 .+-. 0.04 and 0.28 .+-. 0.06 torr/ml/min, respectively, in hypoxic rats receiving 0.01 .mu.g PAF or vehicle. The PAF (10-10 to 10-8 g/ml) also reversed hypoxic vasoconstriction in isolated lungs perfused at constant low. Lungs perfused with salt solution but not those with blood became rapidly densensitized to PAF-induced vasodilation. After constriction with 10-5 M norepinephrine both acetylcholine (10-7 to 10-6 M) and PAF (10-10 to 10-9 g/ml) dilated intact but not endothelium-denuded pulmonary artery rings. Meclofenamate did not block PAF-induced dilation in either lungs or pulmonary arteries. These results indicate that PAF is a potent, cyclooxygenase-independent, endothelium-dependent, pulmonary vasodilator in the rat. It is unclear whether low concentrations of PAF would have similar effects on the pulmonary circulation of other animals.

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