Tangri K K, Gupta G P, Vrat S
Department of Pharmacology and Therapeutics, King George's Medical College, Lucknow, India.
Naunyn Schmiedebergs Arch Pharmacol. 1989 May;339(5):557-63. doi: 10.1007/BF00167261.
The effects of microinjection of histamine and its antagonists into mesencephalic nucleus dorsalis raphe, were investigated on mean arterial pressure and heart rate in cats to elucidate the nature and role of histaminergic receptors in cardiovascular regulation. Microinjection of histamine (5 and 10 micrograms) into nucleus dorsalis raphe elicited both inhibitory and excitatory cardiovascular responses respectively. On the other hand, microinjection of H2-receptor blocker, cimetidine (10 micrograms) resulted in hypertension and tachycardia while H1-receptor antagonist, mepyramine (10 micrograms) microinjection evoked hypotension and bradycardia. Furthermore, local pretreatment with cimetidine and mepyramine blocked the inhibitory and excitatory cardiovascular responses of graded doses of histamine microinjection. These H1 and H2 receptors are localized in nucleus dorsalis raphe since microinjection of histamine into adjoining neural structures did not evoke any cardiovascular change. Furthermore, both the inhibitory and excitatory cardiovascular responses to histamine microinjection could not be observed in animals with spinal cord transection and in animals pretreated with p-chlorophenylalanine while they could be observed in bilateral cervical vagotomized animals. Thus, it appears that these cardiovascular responses to microinjection of histamine into nucleus dorsalis raphe, are due to modulation of serotonergic bulbospinal influence on sympathetic preganglionic neurones in the spinal cord. Moreover, the excitatory cardiovascular responses of high dose of histamine (10 micrograms) seem to result from a local release of noradrenaline since they were blocked by prior microinjection of guanethidine and piperoxan into nucleus dorsalis raphe. A release of noradrenaline in turn, modulates the activity of the neurones of the nucleus by acting on alpha adrenoceptors and thereby alters the activity of sympathetic preganglionic neurones.(ABSTRACT TRUNCATED AT 250 WORDS)
向猫的中脑背侧缝际核微量注射组胺及其拮抗剂,研究其对平均动脉压和心率的影响,以阐明组胺能受体在心血管调节中的性质和作用。向背侧缝际核微量注射组胺(5微克和10微克)分别引起抑制性和兴奋性心血管反应。另一方面,微量注射H2受体阻滞剂西咪替丁(10微克)导致高血压和心动过速,而微量注射H1受体拮抗剂美吡拉敏(10微克)引起低血压和心动过缓。此外,用西咪替丁和美吡拉敏进行局部预处理可阻断不同剂量组胺微量注射引起的抑制性和兴奋性心血管反应。这些H1和H2受体定位于背侧缝际核,因为向相邻神经结构微量注射组胺未引起任何心血管变化。此外,在脊髓横断的动物和用对氯苯丙氨酸预处理的动物中,未观察到对组胺微量注射的抑制性和兴奋性心血管反应,而在双侧颈迷走神经切断的动物中可以观察到。因此,向背侧缝际核微量注射组胺引起的这些心血管反应似乎是由于5-羟色胺能延髓脊髓通路对脊髓中交感神经节前神经元的影响受到调节。此外,高剂量组胺(10微克)引起的兴奋性心血管反应似乎是由于去甲肾上腺素的局部释放,因为在向背侧缝际核预先微量注射胍乙啶和苄哌苯胺后,这些反应被阻断。去甲肾上腺素的释放反过来通过作用于α肾上腺素能受体调节该核神经元的活性,从而改变交感神经节前神经元的活性。(摘要截短至250字)