Guanethidine‐induced Vasodilatation in the Rabbit, Mediated by Endogenous Histamine

Abstract

1 The effects of guanethidine (0.5-4 mg/kg i.v.) on arterial pressure, hindlimb blood flow and hindlimb vascular resistance (HVR) were studied in unanaesthetized rabbits subjected to 'total' autonomic block. 2 Evidence that this response was mediated by histamine release was that (a) 3H-labelled histamine levels in the hindlimb venous blood rose substantially after guanethidine; (b) infusion of exogenous histamine caused an inhibition of the guanethidine-induced vasodilatation; and (c) competitive antagonism of the response was obtained with the H2-antagonist burimamide. 3 There was good correlation between the [3H]-histamine release and the time course of the vasodilator response. Glyceryl trinitrate infusions that lowered HVR substantially, did not cause release of histamine. 4 Reserpine, desipramine and indomethacin pretreatment did not alter the vasodilator response to guanethidine. 5 The guanethidine vasodilator response was not influenced by the H1-antagonist mepyramine or by the other H2-antagonists, metiamide or cimetidine. The vascular receptors stimulated by endogenous histamine may be distinctive from those stimulated by exogenous histamine, or the action of guanethidine may involve greater production of histamine at an intracellular site that is more readily reached by burimamide than by the other H2-antagonists.

Diagnostik und Therapie des sympathisch unterhaltenen Schmerzes

“…In diesem Zusammenhang ist es bemerkenswert, daß eine IVRS auch noch nach einer Sympathektomie eine langanhaltende Analgesie erzeugen kann [56]. Nach tierexperimentellen Befunden könnte die Vasodilatation auch auf einer Histaminfreisetzung beruhen, da sie auch nach Vorbehandlung mit Reserpin auftrat, dagegen nur Histaminblocker verhindert wurde [1,2].…”

Central endogenous histamine modulates sympathetic outflow through H3receptors in the conscious rabbit

“…This dose of burimamide is 2–3‐fold higher than that required to block depressor responses to histamine 30–40 μ g kg −1 i.v. in the rabbit (Parsons & Owen, 1973; Angus et al ., 1977; 1978). A similar dose of burimamide (6 mg kg −1 i.v.)…”