Fraser D G, Regal J F
Department of Pharmacology, University of Minnesota, Duluth 55812.
Immunopharmacology. 1990 Jan-Feb;19(1):59-68. doi: 10.1016/0162-3109(90)90027-c.
Cleavage of the complement protein C5 by activation of the complement system yields a low molecular weight fragment C5a. Knowledge of the alterations in blood pressure induced by C5a as well as the mediators responsible for the blood pressure changes may provide information concerning the potential role of C5a in the adverse hemodynamic responses associated with complement activation. The purpose of this study was to characterize changes in mean arterial pressure in the guinea pig after intravenous challenge with a combination of guinea pig C5a plus C5a(des-Arg) (C5a/C5a(des-Arg)) and determine the mediators responsible for the transient increase in blood pressure which was observed. Mean arterial pressure was monitored in mechanically ventilated pentobarbital-anesthetized guinea pigs. Intravenous injection of C5a/C5a(des-Arg) consistently caused a marked but transient rise in blood pressure. A transient hypotensive response was also seen with injection of markedly higher doses of guinea pig C5a/C5a(des-Arg). Various pharmacological antagonists were used to determine the mediators responsible for the increase in blood pressure induced by guinea pig C5a/C5a(des-Arg). We found that the LTD4 antagonist L-649,923 did not inhibit the transient rise in blood pressure. However, the cyclooxygenase inhibitor indomethacin inhibited the C5a/C5a(des-Arg)-induced pressor response as did the thromboxane synthetase inhibitor U-63557A and the thromboxane receptor antagonist SQ 29,548. In addition, the C5a/C5a(des-Arg)-induced pressor response was not inhibited by the H1 antagonist pyrilamine, but was inhibited in part by the alpha-adrenergic antagonist phentolamine. Also, the response was reduced in animals depleted of circulating platelets or white blood cells. Thus, the results of our studies suggest that intravenously injected guinea pig C5a/C5a(des-Arg) causes release of the vasoconstrictor thromboxane, most likely from circulating white blood cells or platelets, resulting in a transient rise in blood pressure in the guinea pig. In addition, release of catecholamines may contribute to the pressor response observed.
补体系统激活导致补体蛋白C5裂解，产生低分子量片段C5a。了解C5a诱导的血压变化以及导致血压变化的介质，可能会提供有关C5a在与补体激活相关的不良血流动力学反应中潜在作用的信息。本研究的目的是描述豚鼠静脉注射豚鼠C5a加C5a（去精氨酸）（C5a/C5a（去精氨酸））组合后平均动脉压的变化，并确定导致观察到的血压短暂升高的介质。在机械通气的戊巴比妥麻醉豚鼠中监测平均动脉压。静脉注射C5a/C5a（去精氨酸）始终导致血压显著但短暂升高。注射明显更高剂量的豚鼠C5a/C5a（去精氨酸）也出现短暂的降压反应。使用各种药理学拮抗剂来确定导致豚鼠C5a/C5a（去精氨酸）诱导血压升高的介质。我们发现白三烯D4拮抗剂L-649,923不抑制血压的短暂升高。然而，环氧合酶抑制剂吲哚美辛抑制C5a/C5a（去精氨酸）诱导的升压反应，血栓素合成酶抑制剂U-63557A和血栓素受体拮抗剂SQ 29,548也有此作用。此外，C5a/C5a（去精氨酸）诱导的升压反应不受H1拮抗剂吡苄明抑制，但部分受α-肾上腺素能拮抗剂酚妥拉明抑制。而且，在循环血小板或白细胞耗竭的动物中反应减弱。因此，我们的研究结果表明，静脉注射豚鼠C5a/C5a（去精氨酸）会导致血管收缩剂血栓素释放，最有可能来自循环白细胞或血小板，导致豚鼠血压短暂升高。此外，儿茶酚胺的释放可能导致观察到的升压反应。
