| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | British Journal of Pharmacology | ||||
| Publisher: | WILEY-BLACKWELL | ||||
| Place of Publication: | HOBOKEN | ||||
| Volume: | 171 | ||||
| Number of Issue or Book Chapter: | 16 | ||||
| Page Range: | pp. 3858-3867 | ||||
| Date: | 2014 | ||||
| Institutions: | Medicine > Lehrstuhl für Innere Medizin II | ||||
| Identification Number: |
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| Keywords: | VASCULAR SMOOTH-MUSCLE; OCULAR BLOOD-FLOW; ALPHA(1)-ADRENOCEPTOR SUBTYPES; NITRIC-OXIDE; RESISTANCE ARTERIES; RECEPTOR SUBTYPE; RAT AORTA; CONTRACTILE RESPONSES; DIABETIC-RETINOPATHY; CORONARY-ARTERIES; | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 61281 |
Web of ScienceAbstract
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(-/-), ...
Abstract
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.
Metadata last modified: 19 Dec 2024 08:08
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