Comparison of the effects of IVth ventricular administration of some tryptamine analogues with those of 8‐OH‐DPAT on autonomic outflow in the anaesthetized cat

Abstract

1 The present study compares the effects on representative autonomic outflows of IVth ventricular application of tryptamine analogues which act at 5-HT, receptors with 8-hydroxy-2-(di-npropylamino)tetralin (8-OH-DPAT). 2 Cumulative doses of 8-OH-DPAT, N,N-di-n-propyl-5-carboxamidotryptamine (DP-5-CT) and 5-carboxamidotryptamine (5-CT, 2.5-40 nmol kg-'), sumatriptan (10-160 nmol kg-'), indorenate (100-800nmolkg-'), 5-hydroxytryptamine (5-HT, 20-640nmolkg-') both alone and in the presence of cinanserin (0.1 mg kg-') were given into the IVth ventricle of cats which were anaesthetized with a mixture of a-chloralose and pentobarbitone sodium, neuromuscularly blocked and artificially ventilated. Recordings were made of arterial blood pressure, heart rate, renal, cardiac, splanchnic and phrenic nerve activities, femoral arterial flow, tracheal and intragastric pressures. 3 Central application of each of the agonists evoked significant falls in arterial blood pressure. In addition 8-OH-DPAT, DP-5-CT, 5-CT and 5-HT all evoked a differential inhibition of sympathetic nerve activities, with renal nerve activity being the most sensitive and cardiac nerve activity the least sensitive. In the dose-ranges used, administration of sumatriptan evoked reductions only in renal and splanchnic nerve activities whilst indorenate reduced activity in all three sympathetic nerves to a similar extent.4 The effect of the agonists on heart rate was more inconsistent than the effects on sympathetic outflow. IVth ventricular application of 5-CT and sumatriptan were without effect on heart rate whilst 8-OH-DPAT, DP-5-CT, indorenate and 5-HT alone and in the presence of cinanserin all evoked significant bradycardias. However, whilst atropine partially reversed the bradycardias evoked by 8-OH-DPAT and only slightly reversed those caused by indorenate, atropine was without effect on those evoked by DP-5-CT or 5-HT. 5 None of the analogues tested had significant effects on gut motility, phrenic nerve discharge or tracheal pressure. 8-OH-DPAT, DP-5-CT, indorenate and 5-HT were without effect on femoral arterial conductance. However, following pretreatment with cinanserin, 5-HT evoked a significant reduction in femoral arterial conductance. At its highest dose, sumatriptan evoked a significant increase in femoral arterial conductance as did 5-CT at the 20nmolkg-' dose. 6 It is concluded that the present data support the view that 5-HTIA receptors at the level of the brainstem are involved in the central sympathoinhibitory effects caused by intravenous administration of 5-HTA agonists. Further, brainstem 5-HTIA receptors play an important role in the control of renal sympathetic outflow while brainstem 5-HT2 receptors are involved in the control of skeletal muscle and/or skin blood flow. Selective tryptamine agonists for 5-HTIA receptors differ from non-tryptamine agonists in that they do not cause an increase in central cardiac vagal tone.

Mediation by 5‐HT3 receptors of an excitatory effect of 5‐HT on dorsal vagal preganglionic neurones in anaesthetized rats: an ionophoretic study

“…In this respect, microinjection of 5-HT into the rat DVN activates 5-HTIA receptors to cause cardiac slowing (Sporton et al, 1991) and 5-HT2 receptors to evoke increases in gastric motility and acid secretion (Yoneda & Tache, 1995). Similarly, in cats, IVth ventricular application of 8-OH-DPAT increased the excitability of cardiac but not other central parasympathetic motoneurones (Shepheard et al, 1994 and mimicked by application of the selective agonist 2-methyl-5-HT (Travagli et al, 1992; (Dando et al, 1995) or by stimulation of cardiopulmonary C-fibre afferents in rats (Pires et al, 1995). Electrophysiological studies indicate the existence of both pre-and postsynaptic central 5-HT3 receptors regulating neurotransmitter release and mediating rapid ionotropic neurotransmission, respectively (see Peters et al, 1992).…”

“…This innervation comprises fibres originating in the midline raphe nuclei and parapyramidal nucleus (Haxhiu et al, 1993) and from vagal afferents (Sykes et al, 1994). Data from in vivo studies indicate that activation of 5-HTlA receptors increases the excitability of cardiac vagal motoneurones (Ramage & Fozard, 1987;Bogle et al, 1990;Sporton et al, 1991;Chitravanshi & Calaresu, 1992;Futuro-Neto et al, 1993;Dando et al, 1994;McCall et al, 1994;Shepheard et al, 1994) and pulmonary vagal preganglionic neurones (Bootle et al, 1996). However, the excitation of preganglionic vagal neurones in the DVN of the rat by ionophoretic application of 5-HT in vivo (Wang et al, 1995b) was only partially attenuated by the ionophoretic application of 5-HTlA receptor antagonists.…”

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

“…This presumed sympathetic-vasoconstrictor pathway to skeletal muscle appears to be tonically active because i.v. (Ramage, 1985;1988), IVth ventricular (Shepheard et al, 1994) (Shepheard et al, 1991) and the ventral surface of the medulla (King & Holtman, 1990) (Glennon et al, 1988;Teitler et al, 1990). It is concluded from the present results that the sympathoexcitation along with the rise in blood pressure and the respiratory effects evoked by lateral ventricular administration of 5-HT are mediated by the activation of 5-HT2 receptors located in the forebrain. Further, the ability of cinanserin to cause reductions in cardiac nerve activity and heart rate and an increase in femoral arterial conductance suggests that the 5-HT2 receptors mediating these effects are under tonic activation.…”

5-HT1A/7receptor agonist excites cardiac vagal neurons via inhibition of both GABAergic and glycinergic inputs

“…There are also binding sites for 5-HT 1A/7 agonists in both the NA and the DMV in cats [11] , rats [12,13] , and humans [14] . The activation of central 5-HT 1A/7 receptors caused a vagally-mediated bradycardia in cats [9,[15][16][17][18] and rats [19,20] . The ionophoretic application of 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), an agonist of 5-HT 1A/7 receptors, activated CVPN at larger electrophoretic currents in cats, which was attenuated by the co-application of the 5-HT 1A/7 receptor antagonist WAY-100635 [21] .…”