Evidence that activation of 5‐HT₂ receptors in the forebrain of anaesthetized cats causes sympathoexcitation

Abstract

1 The aim of the present experiments was to determine whether the effects of lateral ventricular application of 5-HT on cardiovascular and respiratory variables in anaesthetized cats are mediated by forebrain 5-HT2 receptors. This was carried out by determining whether the effects of 5-HT are blocked by the 5-HT2 antagonist, cinanserin and if they are mimicked by the selective 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). 2 Cats were anaesthetized with a mixture of ac-chloralose and pentobarbitone sodium, neuromuscularly blocked and artificially ventilated. The following cardiovascular and respiratory variables were recorded: renal, splanchnic and cardiac sympathetic nerve activities, phrenic nerve activity, heart rate, arterial blood pressure, femoral arterial conductance and tracheal pressure. All drugs were administered via the lateral ventricle and the action of these agonists was restricted to forebrain sites by a cannula placed in the Aqueduct of Sylvius. 3 Cumulative doses of 5-HT (10-160 nmol kg-') and DOI (80-320 nmol kg-') injected into the lateral ventricle caused significant increases in blood pressure, heart rate, cardiac and splanchnic sympathetic nerve activity and a decrease in femoral arterial conductance. DOI and 5-HT caused a greater increase in cardiac compared with splanchnic nerve activity and failed to change renal nerve activity. 5-HT but not DOI significantly increased the magnitude and the number of phrenic bursts as well as significantly increasing tracheal pressure. The effects of 5-HT also differed from DOI in that 5-HT evoked maximal pressor and near maximal sympathoexcitatory effects after the first dose, whereas the pressor and sympathoexcitatory effects of DOI were graded over the complete dose-range. 4 The 5-HT2 antagonist, cinanserin (265 nmol kg-', i.c.v.) caused significant falls in blood pressure, heart rate and cardiac nerve activity and an increase in femoral arterial conductance. Splanchnic and renal sympathetic nerve activity, phrenic nerve activity and tracheal pressure were unaffected by cinanserin. After pretreatment with cinanserin all cardiovascular and respiratory effects of 5-HT were significantly attenuated. 5 It is concluded that in the cat, as DOI and 5-HT have similar effects on the cardiovascular variables recorded and as the effects of 5-HT are blocked by cinanserin, 5-HT can act on 5-HT2 receptors located in the forebrain to cause differential sympathoexcitation and a rise in arterial blood pressure. Further, the sympathoexcitatory effects mediated by 5-HT2 receptors located in the forebrain differ from those located in the hindbrain in that they mediate increases in cardiac nerve activity and heart rate and also have no effect on renal nerve activity.

Respiratory and cardiovascular effects of the μ‐opioid receptor agonist [Lys7]dermorphin in awake rats

“…A possible explanation for these apparently conflicting results is that 5‐HT receptors involved in opioid respiratory stimulation are not located in the brainstem but within the forebrain. In this respect, the data from our experiments with ritanserin and metergoline are consistent with observations of Anderson et al , (1995) in that the activation of 5‐HT 2 receptors in the forebrain of anaesthetized cats is excitatory to phrenic motoneurones and increases the rate of respiratory drive. Moreover the combined ritanserin and metergoline data could also indicate that 5‐HT 7 receptors (Jasper et al , 1997) might be involved in respiratory stimulation, although evidence for a role for 5‐HT 7 receptors in respiratory function is still lacking.…”

“…The second is mediated by substance P (SP), and is still effective even when opioids have depressed the respiratory network. A third excitatory input is transmitted by 5‐hydroxytryptaminergic projections which originate in the forebrain or raphe nuclei and activate brainstem respiratory neurones and spinal phrenic motoneurones (Davies et al , 1988; Lindsay & Feldman, 1993; Anderson et al , 1995). Therefore in the present experiments, by using selective substance P (SP) and 5‐hydroxytryptamine (5‐HT) receptor antagonists, the mechanism by which the opioid stimulant effect is produced in the rat has also been investigated.…”

Evidence for a role for central 5‐HT2B as well as 5‐HT2A receptors in cardiovascular regulation in anaesthetized rats

“…These effects of quipazine are blocked by pretreatment with the 5‐HT 2 receptor antagonist cinanserin (Rubin et al ., 1964), given i.c.v. at a dose reported in vivo to block the 5‐HT 2 receptor agonist action of 5‐HT and DOI (Anderson et al ., 1992; 1995), and further, the 5‐HT 2 receptor agonist DOI (see Hoyer & Fozard, 1991) when given i.c.v. was found to cause similar cardiovascular effects to those of quipazine in the present experiments.…”

Involvement of central 5‐HT1A receptors in the reflex activation of pulmonary vagal motoneurones by inhaled capsaicin in anaesthetized cats

“…5-hydroxytryptamine (5-HT) causes an increase in tracheal pressure in anaesthetized cats implicating a role for central 5-HT receptors in the control of pulmonary vagal motoneurones. In this respect 5-HTIA and 5-HT2 receptors and 5-HT pathways are well known to play a role in the control of central respiratory drive (Lalley, 1986;King & Holtman, 1990;Shepheard et al, 1991;Sporton et al, 1991;Anderson et al, 1995) and in the control of cardiac vagal motoneurones, particularly 5-HTA receptors (Ramage & Fozard, 1987;Izzo et al, 1988;Bogle et al, 1990;Sporton et al, 1991;Chitravanshi & Calaresu, 1992;Futuro-Neto et al, 1993;. Hence the present experiments were carried out to investigate whether 5-HTA receptors play a role in the control of the reflex activation of pulmonary vagal motoneurones.…”