Independent regulation of α1 and α2 adrenergic receptor-mediated vasoconstriction in vivo

Background Vascular α 1 and α 2 adrenergic receptors mediate vasoconstriction and are major determinants of peripheral vascular tone. There is a wide variability in vasoconstrictor sensitivity to α 1 and α 2 adrenergic receptor agonists among individuals. In previous studies, this variability was not explained by identified α 1 and α 2 adrenergic receptor genetic variants. Thus, we hypothesized that adrenergic vasoconstrictor sensitivity is determined by shared constrictor mechanisms downstream of the individual receptors and that α 1 and α 2 adrenergic receptor-mediated vasoconstrictor sensitivity would therefore be correlated. Methods Dorsal hand vein responses to increasing doses of the α 1 adrenergic receptor agonist phenylephrine (12-12000ng/min) and the α 2 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% (ED 50 ) of maximum venoconstriction (E max ) for each patient. We examined the correlation between phenylephrine and dexmedetomidine ED so and E max before and after adjustment for covariates (age, sex, ethnicity, BMI, blood pressure, heart rate, and baseline plasma norepinephrine concentrations). Results In 62 patients (36 men, 34 African-American, 28 whites), the median ED 50 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 E max 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 (ED 50 ) to phenylephrine and dexmedetomidine, before and after adjustment for covariates (P>0.30). Conclusion Both phenylephrine and dexmedetomidine produce strong venoconstriction in the dorsal hand vein; however, there is no significant correlation between vascular sensitivity to an α 1 and α 2 adrenergic receptor agonist. These findings suggest the independent regulation of vascular α 1 and α 2 adrenergic receptor-mediated responses.