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.
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.
Shepheard
S L
SL
Academic Department of Pharmacology, Royal Free Hospital School of Medicine, Hampstead, London.
Jordan
D
D
Ramage
A G
AG
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002928:Cinanserin / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D010791:Phrenic Nerve / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists; D013564:Sympathetic Nervous System / Q000187:drug effects; D014132:Trachea / Q000187:drug effects; D014363:Tryptamines / Q000008:administration & dosage / Q000494:pharmacology*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014363:Tryptamines; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002928:Cinanserin