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

Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print Cited Medium: Internet ISSN: 1476-5381 (Electronic) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE

Publication: London : Wiley
Original Publication: London, Macmillian Journals Ltd.

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

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.
(© 2014 The British Pharmacological Society.)

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0 (Adrenergic alpha-1 Receptor Agonists)
0 (Receptors, Adrenergic, alpha-1)
0 (Vasoconstrictor Agents)
1WS297W6MV (Phenylephrine)
76898-47-0 (15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid)

Date Created: 20140423 Date Completed: 20150409 Latest Revision: 20211021

20231215

PMC4128048

10.1111/bph.12743

24749494