Histamine H₃‐receptor stimulation is unable to modulate noradrenaline release by the isolated rat heart during ischaemia‐reperfusion

Abstract

The aim of this study was to evaluate the ability of H3-histaminergic prejunctional receptors to modulate the noradrenaline release induced by myocardial ischaemia in the rat, and the effects of an eventual modulation on haemodynamic, biochemical and electrophysiological parameters. Isolated rat hearts were perfused according to the Langendorff technique. Control hearts (n = 13) were not treated; two groups were treated with the H3-agonist R-alpha-methyl-histamine at 0.3 microM (n = 14) and 1 microM (n = 11) and one group, used as positive control, was treated with the selective alpha 2-agonist Mivazerol at 0.5 microM (n = 14) added to the perfusion medium. Noradrenaline, lactate and transaminase output in the coronary effluent, as well as various haemodynamic and electrophysiological parameters, were measured during global and total ischaemia (30 min) and reperfusion (30 min). alpha 2-receptor stimulation increased ischaemia-induced noradrenaline release during reperfusion (195 +/- 13 vs. 145 +/- 12 pmol.g-1 in control group, P < 0.05). In contrast, R-alpha-methyl-histamine, at both doses, did not significantly modify these parameters. Both treatments did not affect ischaemia- and reperfusion-induced haemodynamic (decrease in heart rate or in left ventricular developed pressure), biochemical (lactate and GOT release) and electrophysiological (arrhythmias or increase in action potential duration) alterations. Unlike other species, the rat appears to be insensitive to H3-histaminergic receptor modulation of ischaemia-induced noradrenaline release, although a modulation can be seen with other prejunctional receptor agonists.

Role of Neuronal KATP Channels and Extraneuronal Monoamine Transporter on Norepinephrine Overflow in a Model of Myocardial Low Flow Ischemia

“…In the rat heart, however, such a prejunctional effect of histamine could not be demonstrated (Mazenot et al, 1999). This has been attributed to an insensitivity of the rat to histamine (McLeod et al, 1994;Mazenot et al, 1999). Therefore, in the current study, we did not determine whether histamine H 3 -receptor activation/blockade modulates sympathetic neurotransmission during low flow ischemia.…”

“…In hypoxic myocardium of humans and guinea pigs, a rise in endogenous histamine release is likely to inhibit noradrenergic overactivity through an activation of inhibitory presynaptic histamine H 3 -receptors of sympathetic nerve terminals (Levi and Smith, 2000). In the rat heart, however, such a prejunctional effect of histamine could not be demonstrated (Mazenot et al, 1999). This has been attributed to an insensitivity of the rat to histamine (McLeod et al, 1994;Mazenot et al, 1999).…”