Analysis of the contractile response to serotonin and tryptamine of isolated dog cerebral, femoral and mesenteric arteries. (25/28)

In helically-cut strips of cerebral arteries isolated from dogs, serotonin, tryptamine, 5-hydroxytryptophan and tryptophan caused a dose-related contraction. The potency was in the order of serotonin greater than tryptamine much greater than 5-hydroxytryptophan = tryptophan. In femoral arterial strips, only serotonin and tryptamine produced contractions. In cerebral arteries, the dose-response curve for serotonin was shifted to the right and downward by treatment with cinanserin, whereas in femoral and mesenteric arteries, the curves were shifted to the right. The contractile response of cerebral arteries to tryptamine was attenuated by cinanserin in concentrations above 10(-7) M; however, 10(-5) M was required to significantly reduce the response of femoral arteries. Phentolamine reduced the contractile response of femoral arteries to tryptamine, but not the response of cerebral arteries. It may be concluded that the different antagonism of cinanserin against the serotonin action on cerebral and femoral arteries is due to the ability of high concentrations of serotonin to induce relaxations of cerebral but not femoral arteries or to the different nature of receptors. Tryptamine appears to elicit contractions of cerebral arteries via a stimulation of tryptamine receptors, but elicit those of femoral arteries via stimulation of both alpha-adrenergic and tryptamine receptors. Whether or not receptors for serotonin and tryptamine are the same was not determined.  (+info)

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. (26/28)

1 The present study compares the effects on representative autonomic outflows of IVth ventricular application of tryptamine analogues which act at 5-HT1 receptors with 8-hydroxy-2-(di-n-propylamino)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-1), sumatriptan (10-160 nmol kg-1), indorenate (100-800 nmol kg-1), 5-hydroxytryptamine (5-HT, 20-640 nmol kg-1) both alone and in the presence of cinanserin (0.1 mg kg-1) were given into the IVth ventricle of cats which were anaesthetized with a mixture of alpha-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-OHDPAT 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 20 nmol kg-1 dose.6. It is concluded that the present data support the view that 5-HT1A receptors at the level of the brainstem are involved in the central sympathoinhibitory effects caused by intravenous administration of 5-HT1A agonists. Further, brainstem 5-HT1A 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-HT1A receptors differ from non-tryptamine agonists in that they do not cause an increase in central cardiac vagal tone.  (+info)

Evidence that activation of 5-HT2 receptors in the forebrain of anaesthetized cats causes sympathoexcitation. (27/28)

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 alpha-chloralose and pentobarbitone sodium, neuromuscularly blocked and artifically 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-1) and DOI (80-320 nmol kg-1) 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-1, i.c.v.) caused significant falls in blood pressure,heart rate and cardiac nerve activity and an increase in femoral arterial conductance. Splanchnic andrenal 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.  (+info)

5-HT2 receptor-controlled modulation of medullary respiratory neurones in the cat. (28/28)

1. The effects of the 5-HT2 receptor agonist alpha-methyl-5-HT were studied on the membrane of expiratory (E2) and post-inspiratory (PI) neurones, by intracellular recordings in the caudal medulla of anaesthetized cats. 2. Ionophoresis of alpha-Me-5-HT depolarized membrane potential and increased action potential frequency in a majority of neurones tested. Depolarization of neurones by alpha-Me-5-HT was accompanied by increased input resistance throughout all phases of the respiratory cycle. These effects were antagonized by ionophoresis of cinanserin, a receptor-blocking agent with high affinity for 5-HT2 receptors. 3. E2 neurones were voltage clamped to measure membrane current changes induced by alpha-Me-5-HT ionophoresis. alpha-Me-5-HT induced a net inward current by reducing inspiratory-phase outward currents and increasing expiratory-phase inward currents. These changes were equivalent with steady membrane depolarization, decreased inspiratory phase membrane hyperpolarization and increased expiratory drive potential recorded from the same neurones in current clamp. 4. The effects of alpha-Me-5-HT are consistent with activation of 5-HT2 receptors on E2 and PI neurones leading to blockade of synaptically activated and persistent conductances to potassium ions.  (+info)