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

ABSTRACT: BACKGROUND AND PURPOSE: The ??-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 ??-adrenoceptor subtypes to adrenergic vasoconstriction of retinal arterioles using gene-targeted mice deficient in one of the three adrenoceptor subtypes (??A-AR(-/-), ??B-AR(-/-) and ??D-AR(-/-) respectively). EXPERIMENTAL APPROACH: Using real-time PCR, mRNA expression for individual ??-adrenoceptor subtypes was determined in murine retinal arterioles. To assess the functional relevance of the three ??-adrenoceptor subtypes for mediating vascular responses, retinal vascular preparations from wild-type mice and mice deficient in individual ??-adrenoceptor subtypes were studied in vitro using video microscopy. KEY RESULTS: Retinal arterioles expressed mRNA for all three ??-adrenoceptor subtypes. In functional studies, arterioles from wild-type mice with intact endothelium responded only negligibly to the ??-adrenoceptor agonist phenylephrine. In endothelium-damaged arterioles from wild-type mice, phenylephrine evoked concentration-dependent constriction that was attenuated by the ??-adrenoceptor blocker prazosin. Strikingly, phenylephrine only minimally constricted endothelium-damaged retinal arterioles from ??B-AR(-/-) mice, whereas arterioles from ??A -AR(-/-) and ??D-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 ??-adrenoceptor-mediated vasoconstriction in murine retinal arterioles is buffered by the endothelium. When the endothelium is damaged, a vasoconstricting role of the ??B-adrenoceptor subtype is unveiled. Hence, the ??B-adrenoceptor may represent a target to selectively modulate retinal blood flow in ocular diseases associated with endothelial dysfunction.


PROVIDER: S-EPMC4128048 | BioStudies | 2014-01-01

REPOSITORIES: biostudies

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