Receptores de la serotonina que inhiben el tono simpático vasopresor en la rata descerebrada y desmedulada / Role of serotonin receptors in vascular tone in the pithed rat

Serotonin (5-hydroxytryptamine; 5-HT) has been shown to produce vascular sympatho-inhibition in a wide variety of isolated blood vessels by activation of prejunctional 5-HT1 receptors. After considering the mechanisms involved in modulating neuroeffector transmission, the present review analyzes the experimental findings identifying the pharmacological profile of the 5-HT receptors that inhibit the sympathetically-induced vasopressor responses in pithed rats. Thus, 5-HT-induced sympatho-inhibition has been shown to be: (i) unaffected by physiological saline or by the selective antagonists ritanserin (5-HT2), MDL72222 (5-HT3) or tropisetron (5-HT3/4); (ii) blocked by methysergide, a non-selective 5-HT1/2 receptor antagonist; and (iii) potently mimicked by 5-carboxamidotryptamine (5-CT), a non-selective 5-HT1 receptor agonist, as well as by the selective agonists 8-OH-DPAT (5-HT1A), indorenate (5-HT1A), CP93,129 (5-HT1B), and sumatriptan (5-HT1B/1D). These findings show the involvement of prejunctional 5-HT1 receptors. With the use of selective antagonists, it has been shown subsequently that the sympatho-inhibition induced by indorenate, CP93, 129, and sumatriptan was selectively antagonized by WAY100635 (5-HT1A), cyanopindolol (5-HT1A/1B), and GR127935 (5-HT1B/1D), respectively. These results demonstrate that the 5-HT1 receptors mediating sympatho-inhibition on the systemic vasculature of pithed rats resemble the pharmacological profile of the 5-HT1A, 5-HT1B, and 5-HT1D subtypes.

Influence of 5-hydroxytryptamine on the pressor responses induced by norepinephrine and electrical sympathetic stimulation in the pithed rat

Serotonin (5-hydroxytryptamine; 5-HT) modifies the responses to several vasoconstrictor stimuli prejunctionally and/or postjunctionally. The pressent study analyzed the effects of 5-HT on the pressor responses induced by norepinephrine (NE) or electrical sympathetic stimulation in pithed rats. Responses to intravenous (i.v.) NE (0.03-3 µg/kg) or electrical stimulation at increasing frequencies (0.1 - 3 Hz) were evaluated before and during continous i.v. infusions of physiological saline (0.01 ml/min) or 5-HT (1 - 10 µg/kg x min). The effects of 5-HT on the tachycardic responses to NE and sympathetic stimulation were studied in parallel. The increases in diastolic blood pressure and heart rate produced by NE were not modified by 5-HT. In contrast, 5-HT significantly and dose-dependently inhibited the increases in diastolic blood pressure but not those in heart rate - produced by stimulation of the appropriate spinal segments. Theses effects of 5-HT were more prononced on the responses to lower frequencies of stimulation. It is suggested that 5-HT inhibits the electrically induced pressor responses by a prejunctional mechanism which would lead to a reduction of neurotransmitter release from the sympathetic nerves supplying the systemic vasculature. The selective stimulation of this inhibitory mechanism might represent a new approach for the development of novel antihypertensive agents