Moderate hypothermia attenuates α1-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 (10−4M) and indomethacin (10−5M), 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.