Analysis of the mechanism of the vasodepressor effect of urocortin in anesthetized rats

• Published in: Pharmacology Vol. 73; no. 4; p. 175
• Main Authors: Abdelrahman, Aly M, Syyong, Harley T T, Tjahjadi, Anindita A G, Pang, Catherine C Y
• Format: Journal Article
• Language: English
• Published: Switzerland 01-03-2005
• Subjects: Anesthesia; Animals; Blood Pressure - drug effects; Corticotropin-Releasing Hormone - administration & dosage; Corticotropin-Releasing Hormone - pharmacokinetics; Dose-Response Relationship, Drug; Drug Administration Schedule; Glyburide - pharmacology; Indomethacin - pharmacology; Infusions, Intravenous; Injections, Intravenous; Male; Methylene Blue - pharmacology; Muscle, Smooth, Vascular - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; Norepinephrine - pharmacology; Rats; Rats, Wistar; Tetraethylammonium - pharmacology; Urocortins; Vasodilation - drug effects; Vasodilation - physiology
• ISSN: 0031-7012
• DOI: 10.1159/000082749

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.