No abstract

1 It has recently been shown that continuous infusions of 5-hydroxytryptamine (5-HT) are able to inhibit, in a dose-dependent manner, the pressor responses induced by preganglionic (T7-Tg) sympathetic stimulation in pithed rats pretreated with desipramine (50 mg kg- ', i.v.). This inhibitory effect, besides being significantly more pronounced at lower frequencies of stimulation (0.03-1 Hz) and devoid of tachyphylaxis, is reversible after interrupting the infusions of 5-HT (up to 5.6 pg kg-' min-'). In the present study we have characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5-HT. 2 The inhibition induced by 5.6 Mg kg-' min-' of 5-HT on sympathetically-induced pressor responses was not blocked after i.v. treatment with physiological saline (1 ml kg-'), ritanserin (0.1 mg kg-'), MDL 72222 (0.15 mg kg-') or tropisetron (3 mg kg-'), which did not modify the sympatheticallyinduced pressor responses per se, but was significantly antagonized by the 5-HTI-like and 5-HT2 receptor antagonist, methysergide (0.3 mg kg-1), which also produced a slight attenuation of the pressor responses to 0.03 and 0.1 Hz per se. 3 Unexpectedly and contrasting with methysergide, the 5-HT,-like and 5-HT2 receptor antagonists, methiothepin (0.01, 0.03 and 0.1 mg kg-') and metergoline (1 and 3 mg kg-'), apparently failed to block the above 5-HT-induced inhibition. Nevertheless, it is noteworthy that these antagonists also blocked the electrically-induced pressor responses per se, presumably by blockade of vascular a,-adrenoceptors and, indeed, this property might have masked their potential antagonism at the inhibitory 5-HTI-like receptors. 4 Consistent with the above findings, 5-carboxamidotryptamine (5-CT, a potent 5-HTI-like receptor agonist), metergoline and methysergide mimicked the inhibitory action of 5-HT with the following rank order of agonist potency: 5CT > > 5-HT > metergoline > methysergide. 5 Taken together, the above results suggest that the inhibitory action of 5-HT on the electricallyinduced pressor responses is primarily mediated by an action on inhibitory prejunctional 5-HTI-like receptors leading to a decrease in the sympathetic nerve discharge. Interestingly, 5-HT-induced excitatory mechanisms could be made manifest once the inhibitory action of 5-HT had been antagonized.