Zwieten, “In vivo characterization of vasodilating muscarinic-receptor subtypes in humans

Abstract The role of muscarinic (M)-receptor subtypes in the regulation of vascular tone has not yet been defined in humans. To analyze the role of M-receptor subtypes in the forearm resistance vasculature of normotensive volunteers (n=20), we infused acetylcholine (ACh) and methacholine (MCh) in the presence of saline and the antagonists atropine (nonselective), pirenzepine (M1 selective), and AF-DX 116 (M2 selective), using automated R-wave-triggered venous occlusion plethysmography. Schild analysis was applied by calculating plasma concentrations of the infused compounds and determining EC,0 values. ACh and MCh both caused dose-dependent vasodilatation, with EC50 values of 537 and 52 nmol/L, respectively. The apparent 10-fold higher potency ofMCh compared with ACh may be explained by rapid degradation ofACh in plasma. The concentration-response curve of MCh was shifted to the right by atropine, pirenzepine