Purchase this article with an account.
V. G. Mayer, J. Wess, F. H. Grus, S. C. Joachim, L. Choritz, N. Pfeiffer, A. Gericke; Cholinergic Dilation of Ophthalmic Arteries Is Abolished in M3, but Retained in M5 Acetylcholine Receptor Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):397.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Disturbed ocular hemodynamics have been implicated in the pathophysiology of various eye diseases including age-related macular degeneration and glaucoma. Acetylcholine regulates perfusion of numerous organs via changes in local blood flow involving muscarinic receptor-induced release of nitric oxide. So far, five muscarinic receptor subtypes (M1-M5) have been identified. However, in ocular arteries, the functional relevance of these subtypes remains unknown at present. Hence, the purpose of this study was to determine the muscarinic receptors mediating cholinergic responses in ophthalmic arteries using mice deficient in M3 (M3R-/-) or M5 (M5R-/-) receptors.
Ophthalmic arteries from M3R-/- (n=11), M5R-/- (n=10), and respective wild-type mice (n=11) were isolated, cannulated with micropipettes and pressurized. Luminal vessel diameter was measured using video microscopy.
After preconstriction with phenylephrine, acetylcholine produced dose-dependent dilation of ophthalmic arteries that was similar in M5R-/- and wild-type mice (44±7% and 56±9% at 100 µM; M5R-/- vs. wild-type mice; P>0.05). These responses were completely blocked by atropine, a non-selective muscarinic receptor antagonist. Strikingly, cholinergic dilation of ophthalmic arteries was abolished in M3R-/- mice. In contrast, deletion of either M3 or M5 receptor did not affect responses to non-muscarinic vasodilators, such as bradykinin or nitroprusside.
These findings provide the first direct evidence that M3 receptors are profoundly involved in cholinergic regulation of diameter in murine ophthalmic arteries. M3 receptor agonists might be therapeutically useful to improve ocular perfusion in pathologic conditions.
This PDF is available to Subscribers Only