Zusammenfassung
PURPOSE. We tested the hypothesis that the M-3 muscarinic acetylcholine receptor subtype mediates cholinergic responses in murine ophthalmic arteries after endothelial removal. METHODS. Muscarinic receptor gene expression was determined in ophthalmic arteries with intact and with removed endothelium using real-time PCR. To examine the role of the M-3 receptor in mediating vascular responses, ...
Zusammenfassung
PURPOSE. We tested the hypothesis that the M-3 muscarinic acetylcholine receptor subtype mediates cholinergic responses in murine ophthalmic arteries after endothelial removal. METHODS. Muscarinic receptor gene expression was determined in ophthalmic arteries with intact and with removed endothelium using real-time PCR. To examine the role of the M-3 receptor in mediating vascular responses, ophthalmic arteries from M-3 receptor-deficient mice (M3R(-/-)) and respective wild-type controls were studied in vitro. Functional studies were performed in nonpreconstricted arteries with either intact or removed endothelium using video microscopy. RESULTS. In endothelium-intact ophthalmic arteries, mRNA for all five muscarinic receptor subtypes was detected, but M-3 receptor mRNA was most abundant. In endothelium-removed ophthalmic arteries, M-1, M-2, and M-3 receptors displayed similar mRNA expression levels, which were higher than those for M-4 and M-5 receptors. In functional studies, acetylcholine evoked vasoconstriction in endothelium-removed arteries from wild-type mice that was virtually abolished after incubation with the muscarinic receptor blocker atropine, indicative of the involvement of muscarinic receptors. In concentration-response experiments, acetylcholine and carbachol concentration-dependently constricted endothelium-removed ophthalmic arteries from wild-type mice, but produced only negligible responses in arteries from M3R(-/-) mice. In contrast, acetylcholine concentration-dependently dilated ophthalmic arteries with intact endothelium from wild-type mice, but not from M3R(-/-) mice. Responses to the nitric oxide donor nitroprusside and to KCl did not differ between ophthalmic arteries from wild-type and M3R(-/-) mice, neither in endothelium-intact nor in endothelium-removed arteries. CONCLUSIONS. These findings provide evidence that in murine ophthalmic arteries the muscarinic M-3 receptor subtype mediates cholinergic endothelium-dependent vasodilation and endothelium-independent vasoconstriction.
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