The effect of intrahypothalamic injection of homodimaprit on blood pressure.. P J Gatti; S B Gertner (1984) Neuropharmacology display abstract
Bilateral injection of the inhibitor of histamine-N-methyltransferase, SKF 91488, which is also known as homodimaprit (5 micrograms), into the preoptic area of the rat produced delayed hypertension, tachycardia and hyperthermia. Some animals exhibited pulmonary edema. These effects were only noted 18-24 hr after an injection and were not an artifact of the injection, since the administration of artificial cerebrospinal fluid produced none of these effects. At the time noted, lesions of the rostral hypothalamus, including the preoptic area, were evident. Injection of a vasopressin antagonist, intravenously, did not lower the blood pressure of the hypertensive animals nor did previous bilateral adrenal demullation prevent or delay the hypertension or tachycardia. Therefore, it does not appear that hypersecretion of either vasopressin or adrenal catecholamines contributed to the cardiovascular effects. Peripheral pretreatment with the sympathetic neurotoxin 6-hydroxydopamine however, did prevent the delayed rise in blood pressure following an injection of homodimaprit. From these studies, it is concluded that the injection of homodimaprit produces lesions in the preoptic area, resulting in hypertension that is maintained by excessive activation of the sympathetic nervous system.
Evidence for a role of endogenous histamine in central cardiovascular regulation: inhibition of histamine-N-methyltransferase by SKF 91488.. M C Klein; S B Gertner (1981) The Journal of pharmacology and experimental therapeutics display abstract
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.