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

Mordechai Muszkat, Daniel Kurnik, Gbenga G. Sofowora, Alastair J.J. Wood, C. Michael Stein

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)251-256
Number of pages6
JournalJournal of Hypertension
Volume29
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • vasoconstriction

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