de Jong W, Sandor P, Cox-van Put J, van den Berg M H, van Giersbergen P L
Rudolf Magnus Institute for Pharmacology, State University of Utrecht, The Netherlands.
Resuscitation. 1989 Dec;18(2-3):173-82. doi: 10.1016/0300-9572(89)90020-8.
A variety of neurotransmitters and neuropeptides appear to participate in the central control mechanisms of arterial blood pressure. Our knowledge of these mechanisms is limited as yet. In the present study the involvement of the opioid peptide beta-endorphin in circulatory homeostasis was studied. Under conditions in which beta-endorphin does not affect basal blood pressure and heart rate this peptide had a pronounced prohypotensive influence in normotensive rats. This was found for two conditions during which circulatory homeostasis was challenged. Firstly, during blood letting in a rat model employed to test blood pressure regulation during hemorrhage, and secondly, for the central hypotensive action of alpha-methyldopa. In the first model hypotension was produced by stepwise bleeding to respectively 80, 60 and 40 mmHg mean arterial pressure. Intracerebroventricular (i.c.v.) administration of an antiserum raised against beta-endorphin or of naloxone (s.c. or i.c.v.) caused a significant increase in the required bleeding volume, whereas an opposite action was observed after the injection of morphine (s.c.) or of beta-endorphin (i.c.v.). The role of beta-endorphin in the hypotensive action of alpha-methyldopa, given intracisternally (i.c.) was evaluated in conscious rats equipped with chronic cannulas. Pretreatment with the opiate antagonist naltrexone (i.c.) caused an inhibition of the hypotension and bradycardia induced by alpha-methyldopa. This effect of the receptor antagonist was mimicked by i.c. administration of a beta-endorphin antiserum. Taken together, these data point to a hypotensive influence exerted by endogenous beta-endorphin under conditions during which circulatory homeostasis are challenged.
多种神经递质和神经肽似乎参与了动脉血压的中枢控制机制。目前我们对这些机制的了解还很有限。在本研究中，我们对阿片肽β-内啡肽在循环稳态中的作用进行了研究。在β-内啡肽不影响基础血压和心率的情况下，该肽在正常血压大鼠中具有明显的降血压作用。这一作用在两种循环稳态受到挑战的情况下被发现。首先，在用于测试出血时血压调节的大鼠模型中放血过程中；其次，在α-甲基多巴的中枢降压作用过程中。在第一个模型中，通过逐步放血使平均动脉压分别降至80、60和40 mmHg来诱导低血压。脑室内（i.c.v.）注射针对β-内啡肽的抗血清或纳洛酮（皮下或脑室内）会导致所需放血量显著增加，而注射吗啡（皮下）或β-内啡肽（脑室内）后则观察到相反的作用。在配备慢性插管的清醒大鼠中，评估了β-内啡肽在脑池内（i.c.）给予α-甲基多巴的降压作用中的作用。用阿片受体拮抗剂纳曲酮（脑室内）预处理可抑制α-甲基多巴诱导的低血压和心动过缓。脑室内注射β-内啡肽抗血清可模拟受体拮抗剂的这一作用。综上所述，这些数据表明，在内源性β-内啡肽在循环稳态受到挑战的情况下发挥了降压作用。
