Friedman Eitan A, Harris Paul A, Wood Alastair J J, Stein C Michael, Kurnik Daniel
Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, 542 RRB, Nashville, TN 37232-6602, USA.
Clin Auton Res. 2009 Aug;19(4):247-54. doi: 10.1007/s10286-009-0014-5. Epub 2009 May 15.
Cold-induced vasoconstriction is mediated in part by selective enhancement of local alpha(2C)-adrenoceptor (alpha(2C)-AR) activity. A common insertion-deletion variant in the alpha(2C)-AR gene (ADRA2C del322-325) results in an approximately 85% reduction of agonist-mediated function in vitro. We tested the hypothesis that individuals with the ADRA2C del322-325 variant have attenuated vasoconstriction in response to cold.
Cutaneous digital blood flow (flux) was measured by laser Doppler flowmetry in a controlled environment at room temperature and during two cycles of graduated local heat and cold exposure in 31 subjects. Temperature-response curves were analyzed to estimate the following measures: E(min) (minimal flux during cooling), and ET(50) and ET(90) (the local temperature at which flux decreased by 50 and 90%, respectively).
We found no significant genotypic differences in E(min) (24.3 +/- 19.5, 30.0 +/- 20.5, and 21.5 +/- 25.9 AU for ins/ins, ins/del, and del/del genotypes, respectively; P = 0.48), ET(50) (25.5 +/- 6.0, 25.1 +/- 6.7, and 25.1 +/- 7.1 degrees C; P = 0.99), or ET(90) (20.5 +/- 4.7, 22.1 +/- 4.0, and 20.8 +/- 6.7 degrees C; P = 0.77) in either the first or second heating and cooling cycle (cycle 1 values presented).
The ADRA2C del322-325 variant did not affect vascular sensitivity to local cold exposure.
冷诱导的血管收缩部分是由局部α（2C）-肾上腺素能受体（α（2C）-AR）活性的选择性增强介导的。α（2C）-AR基因中的一个常见插入-缺失变体（ADRA2C del322-325）导致体外激动剂介导的功能降低约85%。我们检验了这样一个假设，即携带ADRA2C del322-325变体的个体对寒冷的血管收缩反应减弱。
在室温的可控环境中以及在31名受试者进行两个周期的局部渐进性热暴露和冷暴露期间，通过激光多普勒血流仪测量手指皮肤血流量（通量）。分析温度-反应曲线以估计以下指标：E（min）（冷却期间的最小通量）、ET（50）和ET（90）（通量分别下降50%和90%时的局部温度）。
我们发现在第一个或第二个加热和冷却周期（给出的周期1值）中，E（min）（纯合插入/插入、杂合插入/缺失和纯合缺失/缺失基因型分别为24.3±19.5、30.0±20.5和21.5±25.9 AU；P = 0.48）、ET（50）（25.5±6.0、25.1±6.7和25.1±7.1℃；P = 0.99）或ET（90）（20.5±4.7、22.1±4.0和20.8±6.7℃；P = 0.77）在基因型上无显著差异。
ADRA2C del322-325变体不影响血管对局部冷暴露的敏感性。
