Cutaneous blood flow and sweat rate responses to exogenous acetylcholine and methacholine

This study tested the hypothesis that cutaneous vasodilation and sweating responses to exogenous administration of methacholine (MCh) will differ relative to acetylcholine (ACh) administration. Twelve subjects had 4 microdialysis membranes placed in dorsal forearm skin. Two membranes were perfused with ACh (1×10 −7 to 1M), while two were perfused with MCh (1×10 −7 to 1M). Sweat rate (SR) and cutaneous vascular conductance (CVC) were simultaneously monitored over each membrane. Responses from membranes receiving the same drug were averaged. Nonlinear regression curve fitting was used to calculate the dose causing 50% of the maximal response (EC 50 ). The EC 50 for CVC and SR at the MCh sites were significantly lower (P<0.01) relative to the ACh sites. In a follow‐up procedure in 4 subjects, two membranes received the same doses of ACh and MCh as above, while two additional membranes received these doses of ACh and MCh co‐perfused with 10 μM neostigmine (an acetylcholinesterase inhibitor). Neostigmine combined with ACh induced a leftward shift (i.e. a lower EC 50 : P<0.01) of the SR and CVC dose‐response curves when compared to ACh alone. In contrast, neostigmine did not alter the EC 50 of the SR and CVC dose‐response curves of SR or CVC to MCh. These results suggest that MCh causes earlier elevations in SR and CVC relative to ACh due to differences in cholinesterase susceptibility between these drugs. Funded by HL84072 & HL61388