Zusammenfassung
Background and PurposeThe (1)-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 (1)-adrenoceptor subtypes to adrenergic vasoconstriction of retinal arterioles using gene-targeted mice deficient in one of the three adrenoceptor subtypes ((1A)-AR(-/-), ...
Zusammenfassung
Background and PurposeThe (1)-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 (1)-adrenoceptor subtypes to adrenergic vasoconstriction of retinal arterioles using gene-targeted mice deficient in one of the three adrenoceptor subtypes ((1A)-AR(-/-), (1B)-AR(-/-) and (1D)-AR(-/-) respectively). Experimental ApproachUsing real-time PCR, mRNA expression for individual (1)-adrenoceptor subtypes was determined in murine retinal arterioles. To assess the functional relevance of the three (1)-adrenoceptor subtypes for mediating vascular responses, retinal vascular preparations from wild-type mice and mice deficient in individual (1)-adrenoceptor subtypes were studied in vitro using video microscopy. Key ResultsRetinal arterioles expressed mRNA for all three (1)-adrenoceptor subtypes. In functional studies, arterioles from wild-type mice with intact endothelium responded only negligibly to the (1)-adrenoceptor agonist phenylephrine. In endothelium-damaged arterioles from wild-type mice, phenylephrine evoked concentration-dependent constriction that was attenuated by the (1)-adrenoceptor blocker prazosin. Strikingly, phenylephrine only minimally constricted endothelium-damaged retinal arterioles from (1B)-AR(-/-) mice, whereas arterioles from (1A)-AR(-/-) and (1D)-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 ImplicationsThe present study is the first to demonstrate that (1)-adrenoceptor-mediated vasoconstriction in murine retinal arterioles is buffered by the endothelium. When the endothelium is damaged, a vasoconstricting role of the (1B)-adrenoceptor subtype is unveiled. Hence, the (1B)-adrenoceptor may represent a target to selectively modulate retinal blood flow in ocular diseases associated with endothelial dysfunction.
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