Analysis of pulmonary and systemic vascular responses to platelet- activating factor in the cat
Pulmonary and systemic vascular responses to platelet-activating factor (PAF) were investigated in the anesthetized cat. Intravenous injections of PAF decreased arterial pressure, increased pulmonary arterial pressure, and caused small but significant decreases in right and left atrial pressures. A transient increase in cardiac output was followed by a secondary decrease, and heart rate was increased. Pulmonary vascular resistance (PVR) was increased, systemic vascular resistance (SVR) was reduced, and changes in PVR and SVR in response to PAF were blocked by the novel PAF receptor antagonist, BN 50730. Under constant-flow conditions PAF dilated the hindlimb vascular bed in a dose-related manner, whereas in the pulmonary lobar vascular bed, PAF caused dose-related increases in perfusion pressure. Hindlimb and lobar vascular responses to PAF were blocked by BN 50730 in a selective manner, whereas cyclooxygenase inhibitors had no effect on responses to the phospholipid mediator. Hindlimb vasodilator responses to PAF were reduced by N(ω)-nitro-L-arginine in a dose that blocked the response to acetylcholine but did not decrease responses to prostaglandin E1 or nitroprusside. Increases in lobar arterial pressure in response to PAF were not altered by treatment with a thromboxane receptor antagonist, when the lung was perfused with a low-molecular-weight dextran solution, or when ventilation to the lobe was interrupted. These data suggest that the release of cyclooxygenase products, activation of thromboxane A2 receptors, cellular aggregation, release of leukocyte or platelet mediators, or changes in bronchomotor tone do not contribute to the pulmonary vasoconstrictor response to PAF and that the hindlimb vasodilator response to the phospholipid mediator is dependent in part on the release of endothelium-derived relaxing factor.
Bellan, JA; Minkes, RK; Hood, JS; McMahon, TJ; Higuera, TR; Nossaman, BD; McNamara, DB; Kadowitz, PJ
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