5-Hydroxytryptamine 1A receptors inhibit cold-induced sympathetically mediated cutaneous vasoconstriction in rabbits.
5-HT1A receptor agonists lower body temperature. We have investigated whether activation of 5-HT1A receptors inhibits cutaneous sympathetic discharge so that dilatation of the cutaneous vascular bed lowers body temperature by increasing heat transfer to the environment. We measured ear pinna blood flow in conscious rabbits (with chronically implanted Doppler ultrasound flow probes), and postganglionic sympathetic vasomotor nerve activity in anaesthetized rabbits. Recordings from conscious rabbits were made in a cage at 26 degrees C and the rabbit was then transferred to a cage at 10 degrees C. The ear pinna Doppler signal fell from 56 +/- 4 cm s-1 in the 26 degrees C cage to 4 +/- 1 cm s-1 (P < 0.0001, n = 24) after 30 min in the 10 degrees C cage, and body temperature increased from 38.8 +/- 0.2 to 39.0 +/- 0.2 degrees C (P < 0.01, n = 24). The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 mg kg-1 I.V.) reversed the cold-induced fall in ear pinna blood flow (Doppler signal increased from 5 +/- 1 to 55 +/- 8 cm s-1, P < 0.001, n = 7) within 5 min when administered 30 min after transfer to the 10 degrees C cage, and prevented the fall in ear pinna blood flow when administered before the rabbit was transferred to the 10 degrees C cage. Body temperature decreased after administration of 8-OH-DPAT. These changes were abolished by the specific 5-HT1A antagonist WAY-100635 (0.1 mg kg-1 I.V.). In anaesthetized rabbits, 8-OH-DPAT (0.1 mg kg-1 I.V.) reduced resting postganglionic cutaneous sympathetic vasomotor discharge, and prevented the increase normally elicited by cooling the trunk. Our experiments constitute the first demonstration that activation of 5-HT1A receptors powerfully inhibits cold-induced increases in cutaneous sympathetic vasomotor discharge, thereby dilating the cutaneous vascular bed and increasing transfer of heat to the environment.
Ootsuka
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Departments of Physiology and Medicine, Centre for Neuroscience, Flinders University Medical Centre, Bedford Park, Adelaide, South Australia 5042, Australia.
Blessing
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001831:Body Temperature; D003080:Cold Temperature; D003243:Consciousness; D004431:Ear, External / Q000098:blood supply; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012867:Skin / Q000098:blood supply* / Q000294:innervation; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin