Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 372332-6602, USA.
J Hypertens. 2011 Feb;29(2):251-6. doi: 10.1097/HJH.0b013e3283407ffd.
Vascular α1 and α2 adrenergic receptors mediate vasoconstriction and are major determinants of peripheral vascular tone. There is a wide variability in vasoconstrictor sensitivity to α1 and α2 adrenergic receptor agonists among individuals. In previous studies, this variability was not explained by identified α1 and α2 adrenergic receptor genetic variants. Thus, we hypothesized that adrenergic vasoconstrictor sensitivity is determined by shared constrictor mechanisms downstream of the individual receptors and that α1 and α2 adrenergic receptor-mediated vasoconstrictor sensitivity would therefore be correlated.
Dorsal hand vein responses to increasing doses of the α1 adrenergic receptor agonist phenylephrine (12-12 000 ng/min) and the α2 adrenergic receptor agonist dexmedetomidine (0.01-100 ng/min) were measured in healthy individuals using a linear variable differential transformer. From individual dose-response curves, we calculated the dose of phenylephrine and dexmedetomidine that produced 50% (ED50) of maximum venoconstriction (Emax) for each patient. We examined the correlation between phenylephrine and dexmedetomidine ED50 and Emax before and after adjustment for covariates (age, sex, ethnicity, BMI, blood pressure, heart rate, and baseline plasma norepinephrine concentrations).
In 62 patients (36 men, 34 African-American, 28 whites), the median ED50 for dexmedetomidine was 1.32 ng/min [interquartile range (IQR) 0.45-5.37 ng/min] and for phenylephrine 177.8 ng/min (IQR 40.7-436.5 ng/min). The Emax for phenylephrine was 90.8% (82.2-99.6%) and for dexmedetomidine 80.0% (64.7-95.2%). There was no correlation between individual sensitivities (ED50) to phenylephrine and dexmedetomidine, before and after adjustment for covariates (P > 0.30).
Both phenylephrine and dexmedetomidine produce strong venoconstriction in the dorsal hand vein; however, there is no significant correlation between vascular sensitivity to an α1 and α2 adrenergic receptor agonist. These findings suggest the independent regulation of vascular α1 and α2 adrenergic receptor-mediated responses.
血管 α1 和 α2 肾上腺素能受体介导血管收缩，是外周血管张力的主要决定因素。个体对 α1 和 α2 肾上腺素能受体激动剂的血管收缩敏感性存在广泛的可变性。在以前的研究中，这种可变性不能用已识别的 α1 和 α2 肾上腺素能受体遗传变异来解释。因此，我们假设肾上腺素能血管收缩敏感性是由个体受体下游的共同收缩机制决定的，并且 α1 和 α2 肾上腺素能受体介导的血管收缩敏感性因此会相关。
使用线性变量差动变压器测量健康个体对 α1 肾上腺素能受体激动剂苯肾上腺素（12-12000ng/min）和 α2 肾上腺素能受体激动剂右美托咪定（0.01-100ng/min）剂量递增时的背手静脉反应。从个体剂量-反应曲线中，我们计算出每个患者产生最大静脉收缩（Emax） 50%（ED50）的苯肾上腺素和右美托咪定剂量。我们在调整协变量（年龄、性别、种族、BMI、血压、心率和基础血浆去甲肾上腺素浓度）前后检查了苯肾上腺素和右美托咪定 ED50 和 Emax 之间的相关性。
在 62 名患者（36 名男性，34 名非裔美国人，28 名白人）中，右美托咪定的中位 ED50 为 1.32ng/min（四分位距（IQR）0.45-5.37ng/min），苯肾上腺素为 177.8ng/min（IQR 40.7-436.5ng/min）。苯肾上腺素的 Emax 为 90.8%（82.2-99.6%），右美托咪定为 80.0%（64.7-95.2%）。在调整协变量前后，个体对苯肾上腺素和右美托咪定的敏感性（ED50）之间没有相关性（P>0.30）。
苯肾上腺素和右美托咪定都能在手背静脉产生强烈的静脉收缩；然而，血管对 α1 和 α2 肾上腺素能受体激动剂的敏感性之间没有显著相关性。这些发现表明血管 α1 和 α2 肾上腺素能受体介导的反应是独立调节的。
