Department of Anesthesiology and Pain Medicine, School of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
Cryobiology. 2012 Aug;65(1):33-40. doi: 10.1016/j.cryobiol.2012.03.009. Epub 2012 Apr 13.
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.
中度低温（25-31°C）可能对血管张力产生显著影响。我们研究了中度低温改变大鼠胸主动脉中α-肾上腺素受体介导的收缩的细胞机制。通过吲哚美辛抑制环氧化酶；通过 L-NAME 抑制一氧化氮（NO）合酶；通过格列本脲和 TEA 抑制钾通道和内皮衍生超极化因子（EDHF）；通过百日咳毒素抑制 G 蛋白；通过育亨宾抑制α2-肾上腺素能；通过普萘洛尔抑制β-肾上腺素能，评估它们对与中度低温（25°C）联合使用的α1-肾上腺素受体激动剂苯肾上腺素（Phe）的收缩反应的影响。中度低温使内皮完整（E+）和去内皮（E-）主动脉环中 Phe 浓度-反应曲线向右移位。与 38°C 相比，E+环中 Phe 的最大反应在 25°C 时显著降低（P<0.05），而 E-环中没有显著差异。在 E+环中，L-NAME（10⁻⁴ M）和吲哚美辛（10⁻⁵ M）联合预处理后，低温诱导的血管舒张作用减弱（P<0.05），而其他抑制剂则无显著作用。重要的是，在 L-NAME 和吲哚美辛预处理的环中加入 TEA 后，低温诱导的血管舒张作用没有进一步减弱（P>0.05）。通过放射免疫测定法测量的 cGMP 和 cAMP 浓度在 25°C 时与 38°C 相比显著升高（P<0.05），而在 E-环中没有显著差异（P>0.05）。本研究表明，大鼠主动脉内皮在中度低温下受到刺激，并且 NO-cGMP 和前列环素（PGI₂）-cAMP 途径代表低温诱导血管舒张的内皮依赖性机制。相比之下，EDHF 可能与低温诱导的血管舒张无关。
