title: Intrathecal PACAP-38 causes prolonged widespread sympathoexcitation via a spinally mediated mechanism and increases in basal metabolic rate in anesthetized rat.
abstract: The rostral ventrolateral medulla differentially regulates sympathetic output to different vascular beds, possibly through the release of various neurotransmitters and peptides that may include pituitary adenylate cyclase-activating polypeptide (PACAP). An intrathecal administration of PACAP increases splanchnic sympathetic nerve activity and heart rate, but not mean arterial blood pressure. The mechanism behind this response is unknown but may be due to a differential control of sympathetic outflows. In this study we sought 1) to investigate whether intrathecal PACAP differentially affects sympathetic outflow, 2) to determine whether the intrathecal responses to PACAP are solely due to a spinally mediated mechanism, and 3) to determine whether intrathecal PACAP affects metabolic function. Experiments using urethane-anesthetized, vagotomized, ventilated, and paralyzed adult male Sprague-Dawley rats were conducted in this study. Intrathecal injections of PACAP-38 were given, and mean arterial pressure, heart rate, the activity of regional sympathetic nerves, end-tidal CO(2), and core temperature were recorded. The novel findings of this study are that 1) intrathecal PACAP-38 causes a prolonged widespread sympathoexcitation in multiple sympathetic beds, 2) this widespread sympathoexcitation is mediated within the spinal cord itself since spinal transection does not abrogate the response, and 3) that intrathecal PACAP-38 increases basal metabolic rate. Therefore, we conclude that intrathecal PACAP acts in the spinal cord to cause a prolonged widespread sympathoexcitation and that PACAP also causes an increase in basal metabolic rate that includes an increase in brown adipose tissue thermogenesis in our rat preparation.
authors: Australian School of Advanced Medicine, L1, F10A, Macquarie Univ., NSW 2109, Sydney, Australia.
authors: Melissa A
authors: MA
authors: Inglott
authors: Melissa M J
authors: MM
authors: Farnham
authors: Paul M
authors: PM
authors: Pilowsky
mesh_terms: D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects* / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007278:Injections, Spinal; D008297:Male; D023421:Models, Animal; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*; D014474:Unconsciousness / Q000503:physiopathology*
chemical_list: D001786:Blood Glucose; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide