The α₁B -adrenoceptor subtype mediates adrenergic vasoconstriction in mouse retinal arterioles with damaged endothelium

Br J Pharmacol. 2014 Aug;171(16):3858-67. doi: 10.1111/bph.12743.


Background and purpose: The α₁-adrenoceptor family plays a critical role in regulating ocular perfusion by mediating responses to catecholamines. The purpose of the present study was to determine the contribution of individual α₁-adrenoceptor subtypes to adrenergic vasoconstriction of retinal arterioles using gene-targeted mice deficient in one of the three adrenoceptor subtypes (α₁A-AR(-/-), α₁B-AR(-/-) and α₁D-AR(-/-) respectively).

Experimental approach: Using real-time PCR, mRNA expression for individual α₁-adrenoceptor subtypes was determined in murine retinal arterioles. To assess the functional relevance of the three α₁-adrenoceptor subtypes for mediating vascular responses, retinal vascular preparations from wild-type mice and mice deficient in individual α₁-adrenoceptor subtypes were studied in vitro using video microscopy.

Key results: Retinal arterioles expressed mRNA for all three α₁-adrenoceptor subtypes. In functional studies, arterioles from wild-type mice with intact endothelium responded only negligibly to the α₁-adrenoceptor agonist phenylephrine. In endothelium-damaged arterioles from wild-type mice, phenylephrine evoked concentration-dependent constriction that was attenuated by the α₁-adrenoceptor blocker prazosin. Strikingly, phenylephrine only minimally constricted endothelium-damaged retinal arterioles from α₁B-AR(-/-) mice, whereas arterioles from α₁A -AR(-/-) and α₁D-AR(-/-) mice constricted similarly to arterioles from wild-type mice. Constriction to U46619 was similar in endothelium-damaged retinal arterioles from all four mouse genotypes.

Conclusions and implications: The present study is the first to demonstrate that α₁-adrenoceptor-mediated vasoconstriction in murine retinal arterioles is buffered by the endothelium. When the endothelium is damaged, a vasoconstricting role of the α₁B-adrenoceptor subtype is unveiled. Hence, the α₁B-adrenoceptor may represent a target to selectively modulate retinal blood flow in ocular diseases associated with endothelial dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Adrenergic alpha-1 Receptor Agonists / pharmacology
  • Animals
  • Arterioles / drug effects
  • Arterioles / physiopathology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenylephrine / pharmacology
  • Receptors, Adrenergic, alpha-1 / genetics
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Retinal Vessels / drug effects
  • Retinal Vessels / physiopathology*
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology*
  • Vasoconstrictor Agents / pharmacology


  • Adrenergic alpha-1 Receptor Agonists
  • Receptors, Adrenergic, alpha-1
  • Vasoconstrictor Agents
  • Phenylephrine
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid