title: Analysis of the mechanism of the vasodepressor effect of urocortin in anesthetized rats.
abstract: The aim was to examine if the depressor effect of urocortin involves activation of the nitric oxide (NO)/L-arginine pathway, production of prostanoids or opening of K(+)-channels. I. v. bolus urocortin (0.1-3 nmol/kg) dose-dependently decreased mean arterial pressure in thiobutabarbital-anesthetized rats. The depressor effect of urocortin was unaffected by pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, inhibitor of NO synthase, i.v. bolus) or noradrenaline (i.v. infusion), which increased arterial pressure to a similar level as that produced by L-NAME. In addition, methylene blue (inhibitor of soluble guanylyl cyclase, i.v. infusion), indomethacin (cyclooxygenase inhibitor, i.v. bolus), glibenclamide (blocker of ATP-sensitive K(+)-channels, i.v. bolus) or tetraethylammonium (a non specific K(+)-channel blocker, i.v. bolus) did not affect the depressor effect of urocortin. In conclusion, the depressor effect of urocortin in anesthetized rats is not mediated via the NO/L-arginine pathway, activation of soluble guanylyl cyclase, production of prostanoids, opening of TEA sensitive K(+)-channels nor opening of ATP sensitive K(+)-channels.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Aly M
authors.initials: AM
authors.lastname: Abdelrahman
authors.forename: Harley T T
authors.initials: HT
authors.lastname: Syyong
authors.forename: Anindita A G
authors.initials: AA
authors.lastname: Tjahjadi
authors.forename: Catherine C Y
authors.initials: CC
authors.lastname: Pang
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005905:Glyburide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D054832:Urocortins; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D054832:Urocortins; D019789:Tetraethylammonium; D003346:Corticotropin-Releasing Hormone; D005905:Glyburide; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin