Platelet-activating factor causes pulmonary vasodilation in the rat.
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, 0.1, and 1.0 microgram 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 microgram 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 microgram PAF or vehicle. The PAF (10(-10) to 10(-8) g/ml) also reversed hypoxic vasoconstriction in isolated lungs perfused at constant flow. Lungs perfused with salt solution but not those with blood became rapidly densensitized to PAF-induced vasodilation. After constriction with 10(-6) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output; D006339:Heart Rate; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D010972:Platelet Activating Factor / Q000502:physiology*; D011651:Pulmonary Artery / Q000502:physiology*; D011652:Pulmonary Circulation; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance; D014661:Vasoconstriction; D014664:Vasodilation
D010972:Platelet Activating Factor; D002245:Carbon Dioxide; D008469:Meclofenamic Acid; D010100:Oxygen