EVIDENCE FOR A ROLE OF ENDOGENOUS HISTAMINE IN CENTRAL CARDIOVASCULAR REGULATION - INHIBITION OF HISTAMINE-N-METHYLTRANSFERASE BY SKF-91488

  • 1 January 1981
    • journal article
    • research article
    • Vol. 216  (2) , 315-320
Abstract
Whether changes in endogenous brain histamine levels would occur concomitant with centrally mediated cardiovascular responses was studied. All experiments were performed on conscious rats, since previous findings have indicated that anesthesia alters cardiovascular responses. Rats were injected intracerebroventricularly (i.c.v.) with SKF 91488 [S-[4-(N,N-dimethylamino)-butyl]isothiourea] (10-100 .mu.g), 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 .mu.g). 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. Cardiovascular resonses after i.c.v. injection of histamine were potentiated by prior treatment with SKF 91488. Brain histamine is involved in central cardiovascular regulation and the hypothalamus may be a site of action. A neurotransmitter role for histamine in the mammalian brain is implied.