Studies on the desensitization of the central cardiovascular responses of histamine.

Intraventricular administration of histamine (HA) in conscious freely moving rats produces a dose-dependent pressor response and bradycardia. These responses are diminished profoundly when a second injection of HA is given within a short time after the first injection. In this study, the specific HA H1 agonist, pyridylethylamine, and the specific H2 agonist, impromidine, were used to examine the nature of this tachyphylaxis. Blood pressure and heart rate were measured directly from indwelling carotid catheters, and drugs were administered in three consecutive intraventricular injections to conscious freely moving rats at 30-min intervals. HA, the H2 agonist, impromidine and the combined injection of pyridylethylamine and impromidine induced tachyphylaxis of the pressor response. The H1 agonist, pyridylethylamine and the HA-N-methyltransferase inhibitor, SKF-91488 (homodimaprit) did not show tachyphylaxis. Heart rate responses were more complex and only HA demonstrated tachyphylaxis of the bradycardia. It is concluded that the tachyphylaxis of the pressor response caused by repeated injections of HA results from the desensitization of central HA H2 receptors.