Role of Histamine H3 Receptors during Ischemia/Reperfusion in Isolated Rat Hearts

Abstract

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.

Regulation of Norepinephrine Release from Isolated Bovine Irides by Histamine

“…Histamine caused a concentrationdependent attenuation of electrically-evoked [ 3 H]NE release without affecting basal tritium efflux. A similar effect of histamine on the release of NE has been reported in human cerebrocortical slices [31], longitudinal muscle-myenteric plexus preparations of guineapig ileum [17], porcine nasal mucosa [32] and heart [33]. The observed ability of histamine to attenuate field-stimulated [ 3 H]NE release in our study indicates that the prejunctional heteroreceptors (localized on sympathetic nerves) regulating the release of NE in bovine irides are inhibitory in nature.…”

Effect of thioperamide on oxidative stress markers in middle cerebral artery occlusion model of focal cerebral ischemia in rats

“…[32][33][34][35][36][37][38][39][40] Recently, we have reported an antioxidant potential of THP, a selective H 3 receptor antagonist, in forced swim test (FST)-induced oxidative stress in mice. 13 Furthermore, in view of the recent evidences for the role of histamine and histaminergic agents in cerebral ischemia, [5][6][7]41 we evaluated the role of THP in the present model. Pretreatment with THP (at both 5.5 and 11 mg/kg i.p.)…”

Different Contributions of Endothelin-A and Endothelin-B Receptors in Postischemic Cardiac Dysfunction and Norepinephrine Overflow in Rat Hearts

“…20,23,24 Most recently, we found that the attenuation of NE overflow after ischemia/reperfusion resulted in a marked improvement in postischemic cardiac dysfunction in isolated rat hearts. 33 Several investigations have also indicated that there is a direct correlation between NE release and the severity of reperfusion arrhythmia in postischemic guinea pig, 23 rat, 43 and mouse 44 hearts. Furthermore, it has been demonstrated that increased plasma NE levels in patients with asymptomatic left ventricular dysfunction appear to predict all-cause and cardiovascular mortality and the development of clinical events related to the onset of heart failure or acute ischemic syndromes.…”

“…Hearts were rapidly excised, connected via the aorta to Langendorff apparatus (IPH-W2, Labo Support), and perfused in a retrograde manner at a constant pressure of 80 mm Hg with perfusate (KrebsHenseleit solution) of the following composition (mmol/L): NaCl 118.1, KCl 4.6, CaCl 2 2.5, MgSO 4 1.2, KH 2 PO 4 1.2, NaHCO 3 24.8, glucose 10. 33 The perfusate was bubbled continuously with a gas mixture of 95% O 2 /5% CO 2 (pH 7.4), and the temperature was maintained at 37°C throughout the experiment. A latex balloon filled with water was inserted into the left ventricle through the left atrium and attached to a pressure transducer (DX-360, Nihon Kohden).…”