title: Moderate hypothermia attenuates α(1)-adrenoceptor-mediated contraction in isolated rat aorta: the role of the endothelium.
abstract: Moderate hypothermia (25-31 °C) may have a significant influence on vascular tone. We investigated the cellular mechanisms by which moderate hypothermia alters α-adrenoceptor-mediated contraction in rat thoracic aortae. Cyclooxygenase inhibition by indomethacin; nitric oxide (NO) synthase inhibition by L-NAME; potassium channel and endothelium-derived hyperpolarizing factor (EDHF) inhibition by glibenclamide and TEA; G protein inhibition by pertussis toxin; α₂-adrenergic inhibition by yohimbine; and β-adrenergic inhibition by propranolol were assessed for their effect on the contractile response to the α1-adrenoceptor agonist phenylephrine (Phe) in combination with moderate hypothermia (25 °C). Moderate hypothermia produced a shift to the right for the Phe concentration-response curves in endothelium-intact (E+) and endothelium-denuded (E-) aortic rings. The maximal response to Phe in E+ rings was significantly decreased (P<0.05) at 25 °C compared to 38 °C, whereas there was no significant difference in E- rings. Hypothermia-induced vasorelaxation in E+ rings was attenuated (P<0.05) following combined pretreatment with L-NAME (10⁻⁴ M) and indomethacin (10⁻⁵ M), whereas other inhibitors had no significant effect. Importantly, the addition of TEA to rings that were pretreated with L-NAME and indomethacin exhibited no further attenuation (P>0.05) of hypothermia-induced vasorelaxation. The concentrations of cGMP and cAMP, as measured by radioimmunoassay, were significantly increased (P<0.05) in E+ rings at 25 °C compared to those at 38 °C, whereas there were no significant differences (P>0.05) in E- rings. The present study demonstrated that rat aortic endothelium is stimulated during moderate hypothermia and that the NO-cGMP and prostacyclin (PGI₂)-cAMP pathways represent endothelium-dependent mechanisms of hypothermia-induced vasorelaxation. In contrast, EDHF may not be associated with hypothermia-induced vasorelaxation.
authors.affiliation: Department of Anesthesiology and Pain Medicine, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Chung
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Hyuk-Jun
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Seok-Young
authors.initials: SY
authors.lastname: Song
authors.forename: Si-Oh
authors.initials: SO
authors.lastname: Kim
authors.forename: Woon-Seok
authors.initials: WS
authors.lastname: Roh
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001685:Biological Factors / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism; D007036:Hypothermia, Induced / Q000379:methods*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D015398:Signal Transduction; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D001685:Biological Factors; D004791:Enzyme Inhibitors; D018340:Receptors, Adrenergic, alpha-1; C067410:endothelium-dependent hyperpolarization factor; D010656:Phenylephrine; D009569:Nitric Oxide; D011464:Epoprostenol; D000242:Cyclic AMP; D051571:Protein Kinase C-alpha; D006152:Cyclic GMP