Kinjo N, Noguchi K, Hirayama K, Sakanashi M
Department of Pharmacology, School of Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Jpn J Pharmacol. 1990 Oct;54(2):151-61. doi: 10.1254/jjp.54.151.
Characteristics of the cardiovascular effects of habu venom were studied in vivo and in vitro in rats. Aortic pressure (AoP), heart rate (HR) and renal cortical blood flow (RCBF) assessed by a laser-Doppler flowmeter were measured in anesthetized rats. Administration of habu venom (0.2-1.6 mg/kg, i.v.) dose-dependently produced a fall in AoP without a marked change in HR. RCBF decreased significantly along with the decline in AoP. Heated habu venom (70 degrees C for 5 min) or the residual venom by dialysis produced similar hemodynamic responses to nonheated crude habu venom. Although habu antivenin significantly reduced the effects of habu venom, indomethacin, aprotinin, atropine, captopril and chlorpheniramine did not. Methylprednisolone significantly attenuated these effects. Habu venom (10(-5) to 3 x 10(-4) g/ml) produced dose-dependent relaxations of the isolated rat aorta preparations precontracted with norepinephrine or KCl, which were not affected by indomethacin, nordihydroguaiaretic acid, p-bromophenacyl bromide, mepacrine, methylene blue or de-endothelialization. These results indicate that habu venom, particularly its heat-stable component(s) which has at least more than 10,000 molecular weight, produces hypotensive and vasorelaxant effects in rats, and suggest that eicosanoids, kinins, histamine, ACh, and endothelium are scarcely involved in these effects.
在大鼠体内和体外研究了蝮蛇毒对心血管系统的影响特性。在麻醉大鼠中,通过激光多普勒血流仪测量主动脉压力(AoP)、心率(HR)和肾皮质血流量(RCBF)。静脉注射蝮蛇毒(0.2 - 1.6 mg/kg)可使AoP呈剂量依赖性下降,而HR无明显变化。随着AoP的下降,RCBF显著降低。加热后的蝮蛇毒(70℃,5分钟)或经透析后的残余毒液产生的血流动力学反应与未加热的粗蝮蛇毒相似。虽然蝮蛇抗毒素可显著降低蝮蛇毒的作用,但吲哚美辛、抑肽酶、阿托品、卡托普利和氯苯那敏则无此作用。甲基泼尼松龙可显著减弱这些作用。蝮蛇毒(10^(-5)至3×10^(-4) g/ml)可使预先用去甲肾上腺素或氯化钾预收缩的离体大鼠主动脉制剂产生剂量依赖性舒张,吲哚美辛、去甲二氢愈创木酸、对溴苯甲酰溴、米帕林、亚甲蓝或去内皮处理对此无影响。这些结果表明,蝮蛇毒,特别是其热稳定成分(分子量至少超过10,000)在大鼠中产生降压和血管舒张作用,并提示类花生酸、激肽、组胺、乙酰胆碱和内皮细胞几乎不参与这些作用。