Role of histamine H3 receptors during ischemia/reperfusion in isolated rat hearts.
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.
Yamamoto
Satoshi
S
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
Tamai
Isao
I
Takaoka
Masanori
M
Matsumura
Yasuo
Y
D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003891:Desipramine / Q000627:therapeutic use*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000502:physiology*
D018759:Adrenergic Uptake Inhibitors; D017442:Histamine Agonists; D006633:Histamine Antagonists; D018100:Receptors, Histamine H3; D003891:Desipramine; D009638:Norepinephrine