Mechanism of pressor effect of 5,6-dihydroxytryptamine in pithed rats

Abstract

5,6-dihydroxytryptamine (5,6-DHT) — a neurotoxic drug causing a chemical degeneration of 5-hydroxytryptamine (5-HT) neurones in brain and to a lesser extend of peripheral adrenergic neurones—provokes a dose-dependent increase in the blood pressure of pithed rats after its intravenous injection. Although the noradrenaline content of the heart, spleen, rectum, and vas deferens is reduced by 50–68% 3 h after the i.p. injection, an indirect sympathomimetic effect does not contribute to the pressor effectof 5,6-DHT. Furthermore, 5,6-DHT does not directly interact with adrenoceptors of the cardiovascular system. The pressor effect of 5,6-DHT thus rests solely on a direct stimulation of 5-HT receptors. The following findings support these statements: 1. Neither pretreatment with reserpine nor application of cocaine attenuates the pressor effect of 5,6-DHT. 2. 2 [β-(4-Hydroxyphenyl)-ethyl-aminomethyl]-tetralone, a selective blocker for α-adrenoceptors, does not alter the effect of 5,6-DHT. 3. The non-competitive 5-HT antagonist phentolamine inhibits the 5,6-DHT effect in a non-competitive manner. 4. The selective, competitive 5-HT antagonist methysergide inhibits the pressor effect of 5,6-DHT in a competitive fashion. Neither pretreatment with reserpine nor application of cocaine attenuates the pressor effect of 5,6-DHT. 2 [β-(4-Hydroxyphenyl)-ethyl-aminomethyl]-tetralone, a selective blocker for α-adrenoceptors, does not alter the effect of 5,6-DHT. The non-competitive 5-HT antagonist phentolamine inhibits the 5,6-DHT effect in a non-competitive manner. The selective, competitive 5-HT antagonist methysergide inhibits the pressor effect of 5,6-DHT in a competitive fashion.

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