Sympathetic Histamine Research Articles

Arrhythmogenic Effect of Sympathetic Histamine in Mouse Hearts Subjected to Acute Ischemia

The role of histamine as a newly recognized sympathetic neurotransmitter has been presented previously, and its postsynaptic effects greatly depended on the activities of sympathetic nerves. Cardiac sympathetic nerves become overactivated under acute myocardial ischemic conditions and release neurotransmitters in large amounts, inducing ventricular arrhythmia. Therefore, it is proposed that cardiac sympathetic histamine, in addition to norepinephrine, may have a significant arrhythmogenic effect. To test this hypothesis, we observed the release of cardiac sympathetic histamine and associated ventricular arrhythmogenesis that was induced by acute ischemia in isolated mouse hearts. Mast cell-deficient mice (MCDM) and histidine decarboxylase knockout (HDC(-/-)) mice were used to exclude the potential involvement of mast cells. Electrical field stimulation and acute ischemia-reperfusion evoked chemical sympathectomy-sensitive histamine release from the hearts of both MCDM and wild-type (WT) mice but not from HDC(-/-) mice. The release of histamine from the hearts of MCDM and WT mice was associated with the development of acute ischemia-induced ventricular tachycardia and ventricular fibrillation. The incidence and duration of induced ventricular arrhythmias were found to decrease in the presence of the selective histamine H(2) receptor antagonist famotidine. Additionally, the released histamine facilitated the arrhythmogenic effect of simultaneously released norepinephrine. We conclude that, under acute ischemic conditions, cardiac sympathetic histamine released by overactive sympathetic nerve terminals plays a certain arrhythmogenic role via H(2) receptors. These findings provided novel insight into the pathophysiological roles of sympathetic histamine, which may be a new therapeutic target for acute ischemia-induced arrhythmias.

Effects of sympathetic histamine on vasomotor responses of blood vessels in rabbit ear to electrical stimulation

To investigate the effects of histamine receptor antagonists on vasoconstriction induced by electrical stimulation (ES) on posterior auricular nerve, and to explore the pre- and post-synaptic effects of sympathetic histamine on the vasomotor responses of vascular smooth muscle in rabbit ear. ES was applied to posterior auricular nerves of the whole rabbit ear at 10 Hz, 20 Hz and 40 Hz, respectively. Besides, the whole ear was perfused with different histamine receptor antagonists under constant perfusion pressure, and the changes in the flow rate of perfusate were observed. The flow rate of venous outflow was decreased by ES at all the 3 frequencies. The ES-induced vasoconstriction at 20 Hz and 40 Hz could be partly inhibited by H(1) receptor antagonist chlorpheniramine (P < 0.05). After exhaustion of histamine in mast cells by pretreatment with specific mast cell degranulator compound 48/80, chlorpheniramine could still inhibit the ES-induced flow rate reduction. In contrast, H(2) receptor antagonist cimetidine could enhance the 40-Hz ES-induced flow rate reduction (P < 0.05). Moreover, ES-induced vasoconstriction at the 3 frequencies could all be enhanced by H(3) receptor antagonist thioperamide (P < 0.05). Stimulation on the auricular nerve may evoke histamine release from sympathetic nerves rather than from mast cells. Moreover, the functions of sympathetic histamine vary from pre-synaptic modulation to post-synaptic vasoconstriction or vasodilatation, via activation of different histamine receptors.

Alpha2 adrenoceptors modulate histamine release from sympathetic nerves in the guinea pig vas deferens

In our previous studies, we have identified that histamine (HA) is co-released with noradrenaline (NA) from the sympathetic nerve terminals and acts as a novel sympathetic neurotransmitter. However, the modulation of sympathetic HA release by sympathetic prejunctional receptors is still unknown. Therefore, in this study, we explored the modulation effect of α 2 adrenoceptors on sympathetic HA release and the interaction of α 2 adrenoceptors with HA H 3 receptors in vas deferens isolated from guinea pig. The selective α 2 adrenoceptor agonist brimonidine decreased the HA overflow in a concentration-dependent manner and abolished the contractile responses mediated by sympathetic HA release. Yohimbine competitively blocked the effect of brimonidine on HA release. Similarly, the HA H 3 receptor agonist R-(α)-methylhistamine also decreased HA release, and thioperamide blocked the effect of R-(α)-methylhistamine. When used singly, both yohimbine and thioperamide facilitated HA release. In addition, the inhibitory effect of brimonidine on HA release was stronger in the presence of thioperamide, while it was reduced when HA H 3 receptors were activated by R-(α)-methylhistamine. Our findings indicate for the first time that sympathetic HA release is negatively modulated both by prejunctional α 2 receptors and HA H 3 receptors and that these two prejunctional receptors interact with each other in modulating sympathetic HA release.

Sympathetic histamine exerts different pre‐ and post‐synaptic functions according to the frequencies of nerve stimulation in guinea pig vas deferens

Histamine (HA) was found to be present in the sympathetic nerve terminals of guinea pig hearts and vasa deferentia in our previous study; however, little is known about the functions of this neurogenic HA. In this study, we used guinea pig vasa deferentia to investigate the pre- and post-synaptic functions of HA evoked by different frequencies of sympathetic nerve stimulation. We found that sympathetic nerve stimulation could evoke HA release, which was independent to mast cell degranulator compound 48/80 and mast cell stabilizer cromolyn, but was highly sensitive to Na(+) channel blocker tetrodotoxin and chemical sympathectomy with 6-hydroxydopamine. The neurogenically released HA evoked by 12.5 Hz of nerve stimulation activated only pre-synaptic H(3) receptors and mediated pre-synaptic inhibitory effects, while under 25 or 50 Hz stimulation condition, HA simultaneously activated both pre-synaptic H(3) receptors and post-synaptic H(1) receptors. However, the direct contractile responses evoked by sympathetic HA via H(1) receptors were observed at 50 Hz. HA release and HA-mediated contractile responses upon sympathetic nerve stimulation were significantly inhibited by pre-treatment of histidine decarboxylase inhibitor alpha-fluoromethylhistidine. Furthermore, application of exogenous HA could mimic these pre- and post-synaptic effects. Our findings indicate that HA in sympathetic neurons acts as a neurotransmitter and its functions vary from pre-synaptic inhibition, to post-synaptic facilitation, to direct post-synaptic contractile responses according to sympathetic nerve stimulation frequencies.

Histamine in Macaca mulatto monkey cardiac sympathetic nerve system: A morphological and functional assessment

Our previous study demonstrated the co-localization of histamine with norepinephrine (NE) within superior cervical ganglia (SCG), and the release of histamine from sympathetic nerve endings of guinea pig evoked by stimulations. We have now further investigated that whether the histamine can be synthesized, stored and released from the sympathetic nerve systems of Macaca mulatto monkey, and investigated the modulation of the sympathetic endogenous histamine release through histamine H 3 receptor in the monkey cardiac sympathetic nerve system. Double-labeled immunofluorescence technique was applied to investigate co-localization of histamine and NE in SCG of Macaca mulatto monkey. The cardiac sympathetic nerve terminals (synaptosomes) of Macaca mulatto monkey was prepared and depolarized with 50 mmol/L K +. Histamine released from synaptosomes was detected by spectrofluorometer and regulations of histamine release through Ca 2+, Ca 2+-channel blockers, H 3-receptor agonist ( R)-α-methylhistamine and histamine H 3-receptor antagonist, thioperamide were observed. Co-localization of histamine and NE was identified within the same neuron of SCG. Release of histamine was Ca 2+-dependent and inhibited by N-type Ca 2+-channel blocker ω-conotoxin, but not affected by the L-type Ca 2+-channel blocker lacidipine. Compound 48/80, a mast cell releaser, did not affect cardiac synaptosome histamine exocytosis. Cardiac synaptosome histamine release was augmented by the enhanced synthesis of histamine or the inhibition of histamine metabolism. Histamine H 3-receptor activation by ( R)-α- methylhistamine inhibited high K +-evoked histamine release and thioperamide blocked the effects of ( R)-α-methylhistamine. These results firstly showed that histamine co-existed with NE within sympathetic neurons of monkey and the exocytosis of histamine from sympathetic terminals could be regulated by presynaptic histamine H 3 receptors. Sympathetic histamine may act as a neurotransmitter to modulate sympathetic neurotransmission.