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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Steege, Andreas Gericke, Adrian Manicam, Caroline Michel, Martin C. Böhmer, Tobias Pfeiffer, Norbert |
| Description | Author Affiliation: Böhmer T ( Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.) |
| Abstract | BACKGROUND AND PURPOSE: The 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 APPROACH: Using 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 RESULTS: Retinal 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 IMPLICATIONS: The 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. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 16 |
| Volume Number | 171 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2014-08-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Arterioles Physiopathology Endothelium, Vascular Receptors, Adrenergic, Alpha-1 Physiology Retinal Vessels Vasoconstriction 15-Hydroxy-11 Alpha,9 Alpha-(epoxymethano)prosta-5,13-dienoic Acid Pharmacology Adrenergic Alpha-1 Receptor Agonists Animals Drug Effects Mice, Inbred C57BL Mice, Knockout Phenylephrine Genetics Vasoconstrictor Agents Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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