Bellan J A, Minkes R K, Hood J S, McMahon T J, Higuera T R, Nossaman B D, McNamara D B, Kadowitz P J
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Am J Physiol. 1992 Jul;263(1 Pt 2):H234-43. doi: 10.1152/ajpheart.1992.263.1.H234.
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 omega-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.
在麻醉猫身上研究了肺血管和体循环血管对血小板活化因子（PAF）的反应。静脉注射PAF可降低动脉压、升高肺动脉压，并使右心房和左心房压力出现小幅但显著的下降。心输出量先短暂增加，随后继发下降，心率增加。肺血管阻力（PVR）增加，体循环血管阻力（SVR）降低，新型PAF受体拮抗剂BN 50730可阻断PAF引起的PVR和SVR变化。在恒流条件下，PAF以剂量相关的方式扩张后肢血管床，而在肺叶血管床，PAF导致灌注压呈剂量相关增加。BN 50730以选择性方式阻断后肢和肺叶血管对PAF的反应，而环氧合酶抑制剂对磷脂介质的反应无影响。N-ω-硝基-L-精氨酸以能阻断对乙酰胆碱反应但不降低对前列腺素E1或硝普钠反应的剂量，降低了后肢血管对PAF的舒张反应。当肺用低分子量右旋糖酐溶液灌注时，或当肺叶通气中断时，血栓素受体拮抗剂处理不会改变PAF引起的肺叶动脉压升高。这些数据表明，环氧合酶产物的释放、血栓素A2受体的激活、细胞聚集、白细胞或血小板介质的释放或支气管运动张力的变化，均不参与PAF引起的肺血管收缩反应，且后肢血管对磷脂介质的舒张反应部分依赖于内皮源性舒张因子的释放。
