Impact of platelet activating factor on vascular responsiveness in isolated rat lungs

MN Gillespie and BD Bowdy

Platelet activating factor (PAF), a suspected mediator of acute lung injury, has been shown to potentiate contraction in isolated porcine carotid arteries. Such an action of PAF, if it occurred in the pulmonary circulation, could be of significance to the evolution of pulmonary hypertension in acute lung injury. Accordingly, we used isolated rat lungs perfused at a constant flow rate with physiologic salt solution to test the hypothesis that PAF-induced lung injury is associated with pulmonary vascular hyperresponsiveness to constrictor stimuli. PAF in concentrations of 0.1 to 10 ng/ml failed to influence pressor responses evoked by i.a. bolus injections of angiotensin II (Ang II) whereas 1 micrograms/ml of PAF significantly blunted Ang II- induced vasoconstriction. Similarly, 1 micrograms/ml, but not 0.1 ng/ml, of PAF attenuated constriction induced by ventilation with 3% O2. PAF at all concentrations tested failed to influence pressor responses evoked by i.a. bolus injections of KCI. Concentrations of PAF which blunted Ang II and hypoxic responses were associated with increased lung wet-to-dry weight ratios indicative of pulmonary edema. Another agent that provokes edema, cytochalasin B, also increased lung wet-to-dry weight ratios and blunted Ang II-, hypoxia-, and KCI-induced pressor responses. PAF delivered as i.a. bolus injections caused acute vasodilation in preparations preconstricted with Ang II but not in those preconstricted with KCI. Collectively, these observations demonstrate that PAF fails to augment and instead blunts pulmonary vascular responsiveness to pressor stimuli, possibly by mechanisms that relate to PAF-induced edema formation and/or vasodilation.

Volume 236, Issue 2, pp. 396-402, 02/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics

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