R-α-甲基组胺及其前药BP 2.94对犬心脏交感神经刺激的H3组胺能抑制作用的体内证明。

In vivo demonstration of H3-histaminergic inhibition of cardiac sympathetic stimulation by R-alpha-methyl-histamine and its prodrug BP 2.94 in the dog.

作者信息

Mazenot C, Ribuot C, Durand A, Joulin Y, Demenge P, Godin-Ribuot D

机构信息

PCEBM, UFR de Pharmacie, Université Grenoble I, La Tronche, France.

出版信息

Br J Pharmacol. 1999 Jan;126(1):264-8. doi: 10.1038/sj.bjp.0702257.

DOI:10.1038/sj.bjp.0702257

PMID:10051144

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565770/

Abstract

The aim of this study was to investigate whether histamine H3-receptor agonists could inhibit the effects of cardiac sympathetic nerve stimulation in the dog. 2. Catecholamine release by the heart and the associated variation of haemodynamic parameters were measured after electrical stimulation of the right cardiac sympathetic nerves (1-4 Hz, 10 V, 10 ms) in the anaesthetized dog treated with R-alpha-methyl-histamine (R-HA) and its prodrug BP 2.94 (BP). 3. Cardiac sympathetic stimulation induced a noradrenaline release into the coronary sinus along with a tachycardia and an increase in left ventricular pressure and contractility without changes in mean arterial pressure. Intravenous administration of H3-receptor agonists significantly decreased noradrenaline release by the heart (R-HA at 2 micromol kg(-1) h(-1): +77 +/- 25 vs +405 +/- 82; BP 2.94 at 1 mg kg(-1): +12 +/- 11 vs +330 +/- 100 pg ml(-1) in control conditions, P < or = 0.05), and increases in heart rate (R-HA at 2 micromol kg(-1) h(-1): +26 +/- 8 vs +65 +/- 10 and BP 2.94 at 1 mg kg(-1): +30 +/- 8 vs 75 +/- 6 beats min(-1), in control conditions P < or = 0.05), left ventricular pressure, and contractility. Treatment with SC 359 (1 mg kg(-1)) a selective H3-antagonist, reversed the effects of H3-receptor agonists. Treatment with R-HA at 2 micromol kg(-1) h(-1) and BP 2.94 at 1 mg kg(-1) tended to decrease, while that with SC 359 significantly increased basal heart rate (from 111 +/- 3 to 130 +/- 5 beats min(-1), P < or = 0.001). 4. Functional H3-receptors are present on sympathetic nerve endings in the dog heart. Their stimulation by R-alpha-methyl-histamine or BP 2.94 can inhibit noradrenaline release by the heart and its associated haemodynamic effects.

摘要

本研究的目的是调查组胺H3受体激动剂是否能抑制犬心脏交感神经刺激的作用。2. 在经R-α-甲基组胺（R-HA）及其前药BP 2.94（BP）处理的麻醉犬中，电刺激右侧心脏交感神经（1-4 Hz，10 V，10 ms）后，测量心脏释放的儿茶酚胺以及血流动力学参数的相关变化。3. 心脏交感神经刺激导致去甲肾上腺素释放到冠状窦，同时伴有心动过速、左心室压力和收缩力增加，平均动脉压无变化。静脉注射H3受体激动剂可显著降低心脏去甲肾上腺素的释放（在2 μmol kg⁻¹ h⁻¹的R-HA作用下：+77 ± 25对比对照条件下的+405 ± 82；在1 mg kg⁻¹的BP 2.94作用下：+12 ± 11对比对照条件下的+330 ± 100 pg ml⁻¹，P ≤ 0.05），以及心率增加（在2 μmol kg⁻¹ h⁻¹的R-HA作用下：+26 ± 8对比对照条件下的+65 ± 10；在1 mg kg⁻¹的BP 2.94作用下：+30 ± 8对比对照条件下的75 ± 6次/分钟，P ≤ 0.05）、左心室压力和收缩力。用选择性H3拮抗剂SC 359（1 mg kg⁻¹）治疗可逆转H3受体激动剂的作用。用2 μmol kg⁻¹ h⁻¹的R-HA和1 mg kg⁻¹的BP 2.94治疗有降低基础心率的趋势，而用SC 359治疗则显著增加基础心率（从111 ± 3次/分钟增至130 ± 5次/分钟，P ≤ 0.001）。4. 犬心脏交感神经末梢存在功能性H3受体。R-α-甲基组胺或BP 2.94对其刺激可抑制心脏去甲肾上腺素释放及其相关的血流动力学效应。