Histamine restores hemorrhage induced hypotension by activating cholinergic neurons in nucleus tractus solitarius

•Histamine clearly reverses hypotension.•Histamine causes the increase ACh and Ch in NTS.•Histamine provides the increase AChE immune reactivity in NTS.•The activation of the central histaminergic receptors, predominantly H1, mediates histamine induced effects.

The purpose of the current study is to investigate the functional connections between the central histaminergic and cholinergic systems at NTS level in hypotensive condition.Experiments were carried out in male Wistar Albino rats. The hypotension was achieved by withdrawing a total volume of 1.5 ml blood/100 g bodyweight over a period of 10 min. A microdialysis study was performed in NTS area to measure extracellular ACh and Ch levels. The hemorrhage produced a severe and long-lasting decrease in mean arterial blood pressure (MAP) and increase in extracellular ACh and Ch levels in NTS. Administration of histamine intracerebroventricularly (i.c.v.) or into the NTS reversed the hemorrhagic hypotension by increasing MAP and heart rate. I.c.v. injection of histamine also caused the additional increase in extracellular ACh and Ch levels. Moreover, central histamine injection augmented intracytoplasmic AChE immunoreactivity in NTS. These changes were completely blocked by histaminergic H1 receptor antagonist chlorpheniramine, but histaminergic H2 receptor blocker ranitidine and histaminergic H3/H4 receptor antagonist thioperamide failed to produce these effects.In conclusion, these findings are interpreted that brain histaminergic H1 receptor activation by central histamine injection may promote cholinergic stimulation in the NTS and subsequently reverses the hypotension.