title: Urotensin-II induces ear flushing in rats.
abstract: OBJECTIVE
  While investigating the effects of systemic urotensin II (U-II), a potent vasoactive peptide acting at the UT receptor, we observed ear pinna flushing after systemic administration to conscious rats. In the present study, U-II-induced ear flushing was quantified in terms of ear pinna temperature change and potential mechanisms were explored.
  
  
  METHODS
  U-II-induced ear flushing was quantified by measuring lateral ear pinna temperature changes and compared to that of calcitonin gene-related peptide (CGRP), a known cutaneous vasodilator. Further, the effects of a variety of pharmacological agents on U-II-induced ear flushing were explored.
  
  
  RESULTS
  Subcutaneous injection of U-II (9 microg kg(-1))produced localized ear pinna flushing with an onset of approximately 15 min, a duration of approximately 30 min and a maximal temperature change of 9 degrees C. In contrast, CGRP caused cutaneous flushing within multiple cutaneous beds including the ear pinna with a shorter onset and greater duration than U-II. A potent UT receptor antagonist, urantide, blocked U-II-induced ear flushing but did not affect CGRP-induced ear flushing. Pretreatment with indomethacin or L-Nomega-nitroarginine methylester (L-NAME) abolished U-II-induced ear flushing. Mecamylamine or propranolol did not affect this response to U-II. Direct intracerebroventricular injection studies suggested that the ear flushing response to U-II was not mediated directly by the CNS.
  
  
  CONCLUSIONS
  Our results suggest that U-II-induced ear flushing and temperature increase is mediated by peripheral activation of the UT receptor and involves prostaglandin- and nitric oxide-mediated vasodilation of small capillary beds in the rat ear pinna.
authors.affiliation: Johnson and Johnson Pharmaceutical Research and Development, Spring House, PA 19477-0776, USA.
authors.forename: J-s
authors.initials: JS
authors.lastname: Qi
authors.forename: R
authors.initials: R
authors.lastname: Schulingkamp
authors.forename: T J
authors.initials: TJ
authors.lastname: Parry
authors.forename: R
authors.initials: R
authors.lastname: Colburn
authors.forename: D
authors.initials: D
authors.lastname: Stone
authors.forename: B
authors.initials: B
authors.lastname: Haertlein
authors.forename: L K
authors.initials: LK
authors.lastname: Minor
authors.forename: P
authors.initials: P
authors.lastname: Andrade-Gordon
authors.forename: B P
authors.initials: BP
authors.lastname: Damiano
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004431:Ear, External / Q000098:blood supply*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005483:Flushing / Q000139:chemically induced*; D007213:Indomethacin / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014579:Urotensins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D018733:Nicotinic Antagonists; D014579:Urotensins; D014665:Vasodilator Agents; D008464:Mecamylamine; C029677:urotensin II; D011433:Propranolol; D052250:Nitric Oxide Synthase Type III; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin