Grässler J, Kühne H, Slepuschkin V D, Zoloev G K, Scheuch D W
Institute of Pathological Biochemistry, Medical Academy, Carl Gustav Carus, Dresden, GDR.
Methods Find Exp Clin Pharmacol. 1988 Dec;10(12):755-60.
The effects of enkephalin derivates with different opioid receptor subtype specificity and naloxone on cardiovascular responses and kallikrein-kinin system (KKS) were studied in anesthetized rats exposed to 30% hemorrhage. Administration of a mu-receptor agonist (DAGO) in early hemorrhage improved mean arterial blood pressure (MAP) responses to hemorrhage. This effect could be abolished by naloxone pretreatment. Moreover, a delayed MAP recovery after hemorrhage could be observed. Treatment with a delta-agonist (DADL) resulted in transient depression of MAP and heart rate (HR). Hemorrhage by itself caused only a slight activation of KKS as indicated by decreased plasma kallikreinogen concentration and reduced kallikrein inhibitor capacity after 20% blood loss. Enkephalin administration did not exert significant effects on KKS. Naloxone pretreatment, in contrast, induced prehemorrhagic activation of KKS, which was potentiated by subsequent hemorrhage. Naloxone-induced activation of KKS could be confirmed by an in vitro study. Taken together these results suggest that the KKS is not involved in MAP and HR responses to enkephalin administration during hemorrhage, whereas it might be implicated in naloxone-induced delayed posthemorrhagic MAP recovery.
在接受30%失血的麻醉大鼠中，研究了具有不同阿片受体亚型特异性的脑啡肽衍生物和纳洛酮对心血管反应及激肽释放酶-激肽系统（KKS）的影响。在出血早期给予μ受体激动剂（DAGO）可改善对出血的平均动脉血压（MAP）反应。这种效应可被纳洛酮预处理消除。此外，可观察到出血后MAP恢复延迟。给予δ激动剂（DADL）导致MAP和心率（HR）短暂降低。如失血20%后血浆激肽释放酶原浓度降低和激肽释放酶抑制能力降低所示，出血本身仅引起KKS轻微激活。给予脑啡肽对KKS无显著影响。相比之下，纳洛酮预处理可诱导出血前KKS激活，随后的出血会使其增强。纳洛酮诱导的KKS激活可通过体外研究得到证实。综合这些结果表明，KKS不参与出血期间脑啡肽给药引起的MAP和HR反应，而它可能与纳洛酮诱导的出血后MAP延迟恢复有关。
