Evidence for a role of endogenous histamine in central cardiovascular regulation: inhibition of histamine-N-methyltransferase by SKF 91488.

Studies were undertaken to determine whether changes in endogenous brain histamine levels would occur concomitant with centrally mediated cardiovascular responses. All experiments were performed on conscious rats since previous findings by others have indicated anesthesia alters cardiovascular responses. Rats were injected intracerebroventricularly (i.c.v.) with SKF 91488 (10-100 micrograms), a potent inhibitor of histamine-N-methyltransferase, while blood pressure and heart rate were recorded. In all animals, there was a dose-related increase in mean arterial blood pressure and a fall in mean heart rate after this treatment. These responses were very similar to the cardiovascular effects observed after i.c.v. injections of exogenous histamine (0.1-5.0 micrograms). Within 5 min after i.c.v. injection of SKF 91488, there was a statistically significant increase in hypothalamic histamine levels; within 15 min, histamine levels were significantly elevated in the cerebral cortex, hypothalamus and the remainder of the brain. In other experiments, cardiovascular responses after i.c.v. injection of histamine were potentiated by prior treatment with SKF 91488. It is concluded that brain histamine is involved in central cardiovascular regulation and that the hypothalamus may be a site of action. These results also imply a neurotransmitter role for histamine in the mammalian brain.