The histaminergic system influences various activities of the central nervous system, including cardiovascular regulation.
Histamine administered intracerebroventricularly (i.c.v.) in anesthetized rats produces the increase in mean arterial pressure (MAP) and heart rate (HR), however, in contrast to normotensive animals,
histamine-induced rises in MAP and HR in critically hypotensive animals are significantly higher. Similarly to exogenous
histamine, inhibition of the central
histamine N-methyltransferase (HNMT) activity (the
enzyme catabolizing
histamine in the central nervous system) resulting in the increase in endogenous
histamine concentration, also leads to the pressor effect in normotensive rats. The present study was designed to determine the role of endogenous central
histamine in cardiovascular regulation in a rat model of blood volume-blood pressure controlled hemorrhagic
hypotension. In normotensive animals, HNMT inhibitor
SKF 91488 produced dose-dependent (20-100 microg i.c.v.) pressor effect accompanied by
tachycardia, similarly as exogenous
histamine (0.5-5 microg i.c.v.) did. The subpressor dose of
SKF 91488 (10 microg) evoked the increase in blood volumes necessary to induce
hypotension of 40 and 20 mmHg and the action was accompanied by the rise in
histamine concentrations in the hypothalamus (5.18 +/- 0.45 vs 4.23 +/- 0.41 nmol/g; p < 0.05) and medulla oblongata (0.41 +/- 0.05 vs 0.30 +/- 0.06 nmol/g; p < 0.05), with no changes in the cortical
histamine concentrations (0.84 +/- 0.18 vs 0.75 +/- 0.17 nmol/g), compared to the control i.c.v. saline-treated group. The effect of
SKF 91488 was inhibited by H1
histamine receptor antagonist
chlorpheniramine, whereas neither H2 receptor blocker
ranitidine, nor
H3 receptor antagonist
thioperamide affected the action. In conclusion, the study demonstrates that the histaminergic system influences the central cardiovascular regulation during pronounced hemorrhagic
hypotension, probably as a result of the activation of compensatory mechanisms.