Characterization of prejunctional 5‐HT receptors mediating inhibition of sympathetic vasopressor responses in the pithed rat

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.

The Dopamine Receptors Mediating Inhibition of the Sympathetic Vasopressor Outflow in Pithed Rats: Pharmacological Correlation with the D2-like Type

“…Moreover, the potentiation of sympathetically-induced vasopressor responses after desipramine made it possible to reveal more marked sympatho-inhibitory responses to quinpirole at lower stimulation frequencies ( fig. 3), as previously shown for other agonists [15,17,18]. This inhibition by quinpirole is not because of tachyphylaxis, as the sympathetic responses remained unchanged in animals receiving saline ( fig.…”

“…4E), which are mainly mediated by a 1 -adrenoceptors [18]. Hence, haloperidol is not appropriate for analysing the pharmacological profile of receptors mediating sympatho-inhibition in our study, as similarly shown for other antagonists [18]. This attenuation by haloperidol could be due to blockade of vascular fig.…”

“…Interestingly, haloperidol (a less selective D 2 -like receptor antagonist; table 1) attenuated per se the sympathetically-induced vasopressor responses ( fig. 4E), which are mainly mediated by a 1 -adrenoceptors [18]. Hence, haloperidol is not appropriate for analysing the pharmacological profile of receptors mediating sympatho-inhibition in our study, as similarly shown for other antagonists [18].…”

“…before each S-R curve to block noradrenaline reuptake. Under these conditions, the vasopressor responses to lower stimulation frequencies are greater than those elicited without desipramine [16][17][18]. After 30 min., baseline values of diastolic blood pressure (a more accurate indicator of peripheral vascular resistance) and heart rate were determined.…”

Post exercise hypotension is not mediated by the serotonergic system in borderline hypertensive individuals

“…11 Centrally administered 8-OH-DPAT, a 5-HT1A receptor agonist, has been shown to decrease blood pressure and sympathetic nerve activity. 12 The sites of 5-HT release in the periphery are the gut and intestines. 13 Both of these areas have minimal blood flow during exercise.…”