Characterization of prejunctional 5‐HT₁ receptors that mediate the inhibition of pressor effects elicited by sympathetic stimulation in the pithed rat

Abstract

1 A study was made of the e ects of 5-carboxamidotryptamine (5-CT) on pressor responses induced in vivo by electrical stimulation of the sympathetic out¯ow from the spinal cord of pithed rats. All animals had been pretreated with atropine. Sympathetic stimulation (0.1, 0.5, 1 and 5 Hz) resulted in frequencydependent increases in blood pressure. Intravenous infusion of 5-CT at doses of 0.01, 0.1 and 1 mg kg 71 min 71 reduced the pressor e ects obtained by electrical stimulation. The inhibitory e ect of 5-CT was signi®cantly more pronounced at lower frequencies of stimulation. In the present study we characterized the pharmacological pro®le of the receptors mediating the above inhibitory e ect of 5-CT. 6 These results suggest that the presynaptic inhibitory action of 5-CT on the electrically-induced pressor response is mediated by both r-5-HT 1D and 5-HT 1A receptors.

5-HT1D receptor inhibits renal sympathetic neurotransmission by nitric oxide pathway in anesthetized rats

“…Furthermore, the most likely locus of the above 5-HT 1D receptors could be prejunctionally on sympathetic periarterial renal nerves. Although we have no direct evidence to unequivocally support this localization, it is noteworthy that L-694,247 failed to affect the vasopressor responses to exogenous norepinephrine (see above), as reported for prejunctional sympathetic-inhibitory 5-HT 1D receptors [9,13,15] in the pithed rat model. Consistent with this suggestion, other findings have detected the presence of 5-HT 1D receptor type in sympathetic nerve endings [32,33], as well as in canine kidney cells [34].…”

“…5-HT seems to modulate adrenergic neurotransmission, leading to sympatho-excitatory or sympatho-inhibitory effects, and, consequently, into vasopressor and tachycardic or vasodepressor and bradycardic responses, respectively [9,13,15,16]. In this sense, some studies by our research team and others have suggested that 5-HT 1 receptor mediates inhibition of the sympathetic neurotransmission [9][10][11][12][13]17,18].…”

“…Furthermore, 5-HT 1D receptors have been mainly shown mediating the inhibition of sympathetically induced tachycardia [38] or vasopressor responses [9,13,15] in pithed rats.…”

“…The doses of all drugs (referring to their free base) were chosen on the basis of our previous experience [9,[11][12][13]15], and taking into account that i) for agonists, the criterion chosen was their pKs, while ii) for antagonists, the doses are always chosen to obtain a minimum of 50% degree of inhibition of the maximum effect evaluated in each experiment: in our experiments, the antagonists reverse the inhibition induced by L-694,247 on the pressor responses induced by electrical stimulation (see Figs. 6 and 7).…”

5-HT Receptor Regulation of Neurotransmitter Release

“…In particular, inhibitory presynaptic 5-HT 1B/1D receptors have been identified on the noradrenergic axon terminals of the cardiovascular system of various species both in vitro and in vivo (Charlton et al, 1986;Göthert et al, 1986;Molderings et al, 1987Molderings et al, , 1990Molderings et al, , 1996Medhurst et al, 1997;Morá n et al, 1998;Harris et al, 2002). Therefore, one could expect that the noradrenergic nerve terminals in the CNS might also be endowed with inhibitory presynaptic 5-HT 1B/1D receptors.…”