title: Cooling augments vasoconstriction mediated by 5-HT1 and alpha2-adrenoceptors in the isolated equine digital vein: involvement of Rho kinase.
abstract: The vasculature of the equine digit fulfils an important role in thermoregulation. In other species, it has been found that cooling may enhance the response of cutaneous vessels to 5-hydroxytryptamine (5-HT) and alpha(2)-adrenoceptor agonists. Translocation of alpha(2)-adrenoceptors to the smooth muscle cell membrane, mediated by Rho kinase, is thought to be involved in the cooling-enhanced response in mouse tail arteries. However, little is known about the effect of cooling on 5-HT receptor function. The present investigation compared the response of 5-bromo-6-(2-imidazolin-2-ylamino) quinoxaline (UK14304:1 nM to 30 microM), methoxamine (0.1 nM to 30 microM; in the presence of yohimbine 0.1 microM), 5-carboxamidotryptamine (5-CT; 0.1 nM to 10 microM) and alpha-methyl 5-HT (0.1 nM to 10 microM) in the isolated equine digital vein at 30 degrees C and 22 degrees C. The effect of the Rho kinase inhibitor, fasudil (1 microM), and the recovery of the response after the irreversible blockade of surface receptors with phenoxybenzamine (10 microM) or 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ;10 microM), was established. Moderate cooling significantly increased the maximum response to alpha-methyl 5-HT, 5-CT and UK14304 and shifted their response curves to the left. Cooling also augmented the phenoxybenzamine- and EEDQ-resistant response to UK14304 and 5-CT, respectively. Fasudil had no effect on the contractile response at 30 degrees C, but completely abrogated the effect of cooling on the response to 5-CT and UK14304. The response to methoxamine was not significantly affected by cooling. These results suggest that Rho kinase plays an important role in the cooling-enhanced response mediated by 5-HT(1B/D) receptors and alpha(2)-adrenoceptors. The exact mechanism by which Rho/Rho kinase enhances the functional responses mediated by these receptors in these vessels has yet to be determined.
authors.affiliation: Department of Veterinary Basic Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK.
authors.forename: Hector
authors.initials: H
authors.lastname: Zerpa
authors.forename: Yoel
authors.initials: Y
authors.lastname: Berhane
authors.forename: Jonathan
authors.initials: J
authors.lastname: Elliott
authors.forename: Simon R
authors.initials: SR
authors.lastname: Bailey
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D000068438:Brimonidine Tartrate; D003080:Cold Temperature; D005534:Foot Diseases / Q000503:physiopathology / Q000662:veterinary; D006614:Hindlimb / Q000098:blood supply; D006734:Horse Diseases / Q000209:etiology / Q000503:physiopathology; D006736:Horses; D008729:Methoxamine / Q000008:administration & dosage / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D047428:Protein Kinase Inhibitors; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; C042390:alpha-methylserotonin; D012701:Serotonin; D000068438:Brimonidine Tartrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C047087:5-carboxamidotryptamine; D054460:rho-Associated Kinases; D008729:Methoxamine; C049347:fasudil