Yamamoto Satoshi, Tamai Isao, Takaoka Masanori, Matsumura Yasuo
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
J Cardiovasc Pharmacol. 2004 Mar;43(3):353-7. doi: 10.1097/00005344-200403000-00005.
Histamine H3 receptors are involved in regulating the release of norepinephrine (NE), in both central and peripheral nervous systems. We investigated the effect of R-alpha-methylhistamine (R-HA), a selective H3 receptor agonist, and thioperamide (Thiop), a selective H3 receptor antagonist, on ischemia/reperfusion-induced changes in carrier-mediated NE release and cardiac function in isolated rat heart. Hearts were subjected to 40-minute ischemia followed by 30-minute reperfusion. Ischemia/reperfusion evoked massive NE release, which was markedly suppressed by the treatment with desipramine (DMI), a neuronal NE transporter blocker. Ischemia/reperfusion-induced cardiac dysfunction (decreases in left ventricular developed pressure, LVDP, and the first derivative of left ventricular pressure, dP/dt, and a rise in left ventricular end diastolic pressure, LVEDP) was also improved by the DMI treatment. The treatment with R-HA also significantly decreased the excessive NE release induced by the ischemia/reperfusion, improved the recovery of LVDP and dP/dt, and suppressed the rise in LVEDP. Thiop did not affect NE release and cardiac function after the reperfusion. When R-HA was administered concomitantly with Thiop, R-HA failed to attenuate ischemia/reperfusion-induced NE release and cardiac dysfunction. Thus, it seems likely that the ischemia/reperfusion-induced carrier-mediated NE release in rat hearts is negatively regulated by the activation of H3 receptors, probably located on cardiac noradrenergic nerve endings.
组胺H3受体参与调节中枢和外周神经系统中去甲肾上腺素（NE）的释放。我们研究了选择性H3受体激动剂R-α-甲基组胺（R-HA）和选择性H3受体拮抗剂硫代哌啶（Thiop）对离体大鼠心脏缺血/再灌注诱导的载体介导的NE释放变化和心脏功能的影响。心脏先进行40分钟的缺血，然后再灌注30分钟。缺血/再灌注引发大量NE释放，而神经元NE转运体阻滞剂地昔帕明（DMI）处理可显著抑制这种释放。DMI处理还改善了缺血/再灌注诱导的心脏功能障碍（左心室舒张末压、LVDP和左心室压力的一阶导数dP/dt降低，左心室舒张末压LVEDP升高）。R-HA处理也显著降低了缺血/再灌注诱导的过量NE释放，改善了LVDP和dP/dt的恢复，并抑制了LVEDP的升高。硫代哌啶对再灌注后的NE释放和心脏功能没有影响。当R-HA与硫代哌啶同时给药时，R-HA未能减轻缺血/再灌注诱导的NE释放和心脏功能障碍。因此，大鼠心脏中缺血/再灌注诱导的载体介导的NE释放似乎可能受到可能位于心脏去甲肾上腺素能神经末梢的H3受体激活的负调节。
