Key result
Deletion of the M3 receptor gene virtually abolished cholinergic dilation in small arteries, whereas M1 and M5 receptor deletion had no effect compared to wild-type mice.
M3 receptors, but not M1 or M5 receptors, are the primary mediators of cholinergic vasodilation in murine cutaneous, skeletal muscle, and renal interlobar arteries.
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M3 predominates in murine cholinergic vasodilation; leaves open receptor identity and therapeutic relevance in human vessels.
Acetylcholine regulates perfusion of numerous organs via changes in local blood flow involving muscarinic receptor-induced release of vasorelaxing agents from the endothelium. The purpose of the present study was to determine the role of M₁, M₃, and M₅ muscarinic acetylcholine receptors in vasodilation of small arteries using gene-targeted mice deficient in either of the three receptor subtypes (M1R(-/-), M3R(-/-), or M5R(-/-) mice, respectively). Muscarinic receptor gene expression was determined in murine cutaneous, skeletal muscle, and renal interlobar arteries using real-time PCR. Moreover, respective arteries from M1R(-/-), M3R(-/-), M5R(-/-), and wild-type mice were isolated, cannulated with micropipettes, and pressurized. Luminal diameter was measured using video microscopy. mRNA for all five muscarinic receptor subtypes was detected in all three vascular preparations from wild-type mice. However, M(3) receptor mRNA was found to be most abundant. Acetylcholine produced dose-dependent dilation in all three vascular preparations from M1R(-/-), M5R(-/-), and wild-type mice. In contrast, cholinergic dilation was virtually abolished in arteries from M3R(-/-) mice. Deletion of either M₁, M₃, or M₅ receptor genes did not affect responses to nonmuscarinic vasodilators, such as substance P and nitroprusside. These findings provide the first direct evidence that M₃ receptors mediate cholinergic vasodilation in cutaneous, skeletal muscle, and renal interlobar arteries. In contrast, neither M₁ nor M₅ receptors appear to be involved in cholinergic responses of the three vascular preparations tested.
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Gericke et al. (2011) studied this question. M1, M3, or M5 receptor gene deletion vs. Wild-type mice was evaluated on Cholinergic vasodilation. Deletion of the M3 receptor gene virtually abolished cholinergic dilation in small arteries, whereas M1 and M5 receptor deletion had no effect compared to wild-type mice.
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