Klein M C, Gertner S B
J Pharmacol Exp Ther. 1981 Feb;216(2):315-20.
Studies were undertaken to determine whether changes in endogenous brain histamine levels would occur concomitant with centrally mediated cardiovascular responses. All experiments were performed on conscious rats since previous findings by others have indicated anesthesia alters cardiovascular responses. Rats were injected intracerebroventricularly (i.c.v.) with SKF 91488 (10-100 micrograms), a potent inhibitor of histamine-N-methyltransferase, while blood pressure and heart rate were recorded. In all animals, there was a dose-related increase in mean arterial blood pressure and a fall in mean heart rate after this treatment. These responses were very similar to the cardiovascular effects observed after i.c.v. injections of exogenous histamine (0.1-5.0 micrograms). Within 5 min after i.c.v. injection of SKF 91488, there was a statistically significant increase in hypothalamic histamine levels; within 15 min, histamine levels were significantly elevated in the cerebral cortex, hypothalamus and the remainder of the brain. In other experiments, cardiovascular responses after i.c.v. injection of histamine were potentiated by prior treatment with SKF 91488. It is concluded that brain histamine is involved in central cardiovascular regulation and that the hypothalamus may be a site of action. These results also imply a neurotransmitter role for histamine in the mammalian brain.
开展了多项研究以确定内源性脑组胺水平的变化是否会与中枢介导的心血管反应同时发生。所有实验均在清醒大鼠身上进行，因为其他人先前的研究结果表明麻醉会改变心血管反应。给大鼠脑室内注射（i.c.v.）组胺-N-甲基转移酶的强效抑制剂SKF 91488（10-100微克），同时记录血压和心率。在所有动物中，这种处理后平均动脉血压呈剂量相关升高，平均心率下降。这些反应与脑室内注射外源性组胺（0.1-5.0微克）后观察到的心血管效应非常相似。脑室内注射SKF 91488后5分钟内，下丘脑组胺水平有统计学意义的升高；15分钟内，大脑皮层、下丘脑和大脑其余部分的组胺水平显著升高。在其他实验中，预先用SKF 91488处理可增强脑室内注射组胺后的心血管反应。得出的结论是，脑组胺参与中枢心血管调节，下丘脑可能是作用部位。这些结果还暗示组胺在哺乳动物大脑中具有神经递质作用。
