Gericke, Adrian and Sniatecki, Jan J. and Goloborodko, Evgeny and Steege, Andreas and Zavaritskaya, Olga and Vetter, Jan M. and Grus, Franz H. and Patzak, Andreas and Wess, Juergen and Pfeiffer, Norbert (2011) Identification of the Muscarinic Acetylcholine Receptor Subtype Mediating Cholinergic Vasodilation in Murine Retinal Arterioles. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 52 (10). pp. 7479-7484. ISSN 0146-0404,
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PURPOSE. To identify the muscarinic acetylcholine receptor subtype that mediates cholinergic vasodilation in murine retinal arterioles. METHODS. Muscarinic receptor gene expression was determined in murine retinal arterioles using real-time PCR. To assess the functional relevance of muscarinic receptors for mediating vascular responses, retinal vascular preparations from muscarinic receptor-deficient mice were studied in vitro. Changes in luminal arteriole diameter in response to muscarinic and nonmuscarinic vasoactive substances were measured by video microscopy. RESULTS. Only mRNA for the M 3 receptor was detected in retinal arterioles. Thus, M 3 receptor-deficient mice (M3R(-/-)) and respective wild-type controls were used for functional studies. Acetylcholine concentration-dependently dilated retinal arterioles from wild-type mice. In contrast, vasodilation to acetylcholine was almost completely abolished in retinal arterioles from M3R(-/-) mice, whereas responses to the nitric oxide (NO) donor nitroprusside were retained. Carbachol, an acetylcholinesterase-resistant analog of acetylcholine, also evoked dilation in retinal arterioles from wild-type, but not from M3R(-/-), mice. Vasodilation responses from wild-type mice to acetylcholine were negligible after incubation with the non-subtype-selective muscarinic receptor blocker atropine or the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester, and were even reversed to contraction after endothelial damage with 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate. CONCLUSIONS. These findings provide evidence that endothelial M 3 receptors mediate cholinergic vasodilation in murine retinal arterioles via activation of NO synthase. (Invest Ophthalmol Vis Sci. 2011;52:7479-7484) DOI:10.1167/iovs.11-7370
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHOROIDAL BLOOD-FLOW; COMMERCIALLY AVAILABLE ANTISERA; KNOCKOUT MICE; NITRIC-OXIDE; ENDOTHELIAL DYSFUNCTION; ISOMETRIC-EXERCISE; INDUCED RELAXATION; VESSELS; PROPRANOLOL; ATROPINE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Jun 2020 08:27 |
| Last Modified: | 02 Jun 2020 08:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20234 |
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