Subtype specific regulation of human vascular α1-adrenergic receptors by vessel bed and age

Academic Article

Abstract

  • Background - α1-adrenergic receptors (α1ARs) regulate blood pressure, regional vascular resistance, and venous capacitance; the exact subtype (α(1a), α(1b), α(1d)) mediating these effects is unknown and varies with species studied. In order to understand mechanisms underlying cardiovascular responses to acute stress and chronic catecholamine exposure (as seen with aging), we tested two hypotheses: (1) human α1AR subtype expression differs with vascular bed, and (2) age influences human vascular α1AR subtype expression. Methods and Results - Five hundred vessels from 384 patients were examined for α1AR subtype distribution at mRNA and protein levels (RNase protection assays, ligand binding, contraction assays). Overall vessel α1AR density is 16±2.3fmol/mg total protein, α(1a)AR predominates in arteries at mRNA (P<0.001) and protein (P<0.05) levels; all 3 subtypes are present in veins. Furthermore, α1AR mRNA subtype expression varies with vessel bed (α(1a) higher in splanchnic versus central arteries, P<0.05); competition analysis (selected vessels) and functional assays demonstrate α(1a) and α(1b)-mediated mammary artery contraction. Overall α1AR expression doubles with age (<55 versus ≥65 years) in mammary artery (no change in saphenous vein), accompanied by increased α(1b)>α(1a) expression (P≤0.001). Conclusions - Human vascular α1AR subtype distribution differs from animal models, varies with vessel bed, correlates with contraction in mammary artery, and is modulated by aging. These findings provide potential novel targets for therapeutic intervention in many clinical settings.
  • Authors

    Published In

  • Circulation  Journal
  • Digital Object Identifier (doi)

    Author List

  • Rudner XL; Berkowitz DE; Booth JV; Funk BL; Cozart KL; D'Amico EB; El-Moalem H; Page SO; Richardson CD; Winters B
  • Start Page

  • 2336
  • End Page

  • 2343
  • Volume

  • 100
  • Issue

  • 23