Gulati A, Rebello S
Department of Pharmacodynamics (m/c 865), University of Illinois at Chicago 60612-7231.
Artif Cells Blood Substit Immobil Biotechnol. 1994;22(3):603-12. doi: 10.3109/10731199409117889.
Diaspirin cross-linked Hemoglobin (DCLHb) (400 mg/kg, i.v.), a resuscitative solution, produces a pressor effect in rats and several other species. Studies were conducted to determine the role of the central nervous system and adrenal medulla in the pressor effect of DCLHb in rats. Intravenous administration of DCLHb produced an increase in blood pressure in cervical sectioned animals, which was comparable to that observed in normal rats. This indicates that the pressor effect of DCLHb was mediated through the peripheral vascular system rather than through the central nervous system. DCLHb produced a pressor effect in bilateral adrenal demedullated rats that was similar to normal rats, suggesting that the pressor effect is not through the release of catecholamines or other pressor substance from the adrenal medulla. The effects of DCLHb pretreatment on norepinephrine (0.5 microgram/kg), phenylephrine (5 micrograms/kg) and clonidine induced blood pressure and heart rate responses were also studied. DCLHb significantly potentiated the pressor response to norepinephrine and phenylephrine. Clonidine normally produces a fall in blood pressure by acting on the central alpha-adrenoceptors, and a rise in blood pressure by stimulating the peripheral vascular alpha-adrenoceptors. DCLHb produced a marked potentiation of the pressor response to clonidine (75 micrograms/kg, i.v.), that masked the central depressor effect. The specificity of the potentiation was confirmed by using phenoxybenzamine, prazosin, and yohimbine. In order to exclude the contribution of a centrally induced cardiovascular effect of clonidine, further studies were carried out in cervical sectioned rats. DCLHb markedly potentiated the pressor effect of clonidine (25 micrograms/kg, i.v.) in cervical sectioned rats. This potentiation could be attenuated by prazosin and yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)
双阿司匹林交联血红蛋白(DCLHb)(400毫克/千克,静脉注射)是一种复苏溶液,在大鼠和其他几种物种中可产生升压作用。进行了多项研究以确定中枢神经系统和肾上腺髓质在DCLHb对大鼠升压作用中的作用。对颈部切断的动物静脉注射DCLHb会导致血压升高,这与在正常大鼠中观察到的情况相当。这表明DCLHb的升压作用是通过外周血管系统介导的,而不是通过中枢神经系统。DCLHb在双侧肾上腺髓质切除的大鼠中产生的升压作用与正常大鼠相似,这表明升压作用不是通过肾上腺髓质释放儿茶酚胺或其他升压物质实现的。还研究了DCLHb预处理对去甲肾上腺素(0.5微克/千克)、去氧肾上腺素(5微克/千克)和可乐定诱导的血压和心率反应的影响。DCLHb显著增强了对去甲肾上腺素和去氧肾上腺素的升压反应。可乐定通常通过作用于中枢α-肾上腺素能受体使血压下降,并通过刺激外周血管α-肾上腺素能受体使血压升高。DCLHb对可乐定(75微克/千克,静脉注射)的升压反应产生了明显的增强作用,掩盖了中枢降压作用。通过使用酚苄明、哌唑嗪和育亨宾证实了这种增强作用的特异性。为了排除可乐定中枢诱导的心血管效应的影响,在颈部切断的大鼠中进行了进一步的研究。DCLHb在颈部切断的大鼠中显著增强了可乐定(25微克/千克,静脉注射)的升压作用。这种增强作用可被哌唑嗪和育亨宾减弱。(摘要截短于250字)