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

Muszkat M, Kurnik D, Sofowora GG, Wood AJ, Stein CM
J Hypertens. 2011 29 (2): 251-6

PMID: 21045729 · PMCID: PMC3012748 · DOI:10.1097/HJH.0b013e3283407ffd

BACKGROUND - 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.

METHODS - 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).

RESULTS - 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).

CONCLUSION - 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.

MeSH Terms (16)

Adrenergic alpha-1 Receptor Agonists Adrenergic alpha-2 Receptor Agonists Adult Dexmedetomidine Dose-Response Relationship, Drug Female Hand Humans Male Models, Cardiovascular Phenylephrine Receptors, Adrenergic, alpha-1 Receptors, Adrenergic, alpha-2 Signal Transduction Vasoconstriction Young Adult

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