Inhibitory 5‐hydroxytryptamine receptors involved in pressor effects obtained by stimulation of sympathetic outflow from spinal cord in pithed rats

Abstract

1 A study was made of the effects of 5-hydroxytryptamine (5-HT) on pressor response induced in vivo by electrical stimulation of the sympathetic outflow from the spinal cord of pithed rats. All animals had been pretreated with atropine. Intravenous infusion of 5-hydroxytryptamine at doses of 10 and 20 jig kg-' min-' reduced the pressor effects obtained by electrical stimulation at intervals of 10 min over the 1 h of infusion. 2 This inhibitory action of 5-HT was depressed by cyproheptadine and methiothepin but was not modified by ketanserin or MDL-72222. By contrast, the inhibitory action of 5-HT was lost in pithed rats that had been pretreated with exogenous noradrenaline.3 The 5-HT, receptor agonist 5-carboxamidotryptamine (5-CT) caused an inhibition of the pressor response, whereas the 5-HT3 receptor agonist, 1-phenylbiguanide, produced a variable but significant increase in the pressor response. The 5-HT2 receptor agonist, m-CPP, did not modify the pressor sympathetic response. 4 Our results suggest that 5-hydroxytryptamine interferes with sympathetic neurotransmission by inhibiting pressor effects as a result of stimulation of the complete sympathetic outflow, and that this inhibition is mainly through a presynaptic 5-HT1 mechanism.

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].…”

“…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).…”

“…Thus, a potential therapeutical target would be the modulation of NE release after increased sympathetic activity; in this line, it has been established that NE release could be regulated by prejunctional receptors, including serotonin receptors [9][10][11][12][13][14]. 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].…”

“…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]. Despite the above findings along with the importance of the renal sympathetic neurotransmission in many cardiovascular diseases, the following, unfortunately, have not yet been determined: i) the effect of serotonin, the endogenous ligand, on the renal noradrenergic neurotransmission and the pharmacological nature of 5-HT receptors involved; ii) the effect of 5-HT 1 receptor subtype agonists on renal sympathetic outflow; and iii) the prejunctional or postjunctional nature of receptors implicated and the possible indirect pathways associated.…”