Submitted on September 22, 2006
Accepted on December 26, 2006
Cutaneous blood flow and sweat rate responses to exogenous administration of acetylcholine and methacholine
Kenichi Kimura1, David A Low2, David M Keller3, Scott L. Davis4, and Craig G. Crandall5*
1 Presbyterian Hospital of Dallas, Institute for Exercise and Environmnental Medicine, Dallas, Texas, United States
2 Institute for Exercise and Environmental Medicine, Dallas, Texas, United States
3 Environmental Physiology, Institute for Exercise and Environmental Medicine, Dallas, Texas, United States
4 Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States
5 Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, Dallas, Texas, United States; Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States
* To whom correspondence should be addressed. E-mail: craigcrandall{at}texashealth.org.
The study evaluated cutaneous vasodilation and sweating to exogenous acetylcholine (ACh) and methacholine (MCh), given differing sensitivity of these substances to endogenous cholinesterase. Four intradermal microdialysis membranes were placed in dorsal forearm skin. Two membranes were perfused with ACh (1*10-7M to 1M), while the other two membranes were perfused with the same concentrations of MCh. Sweat rate (SR) and cutaneous blood flow were simultaneous assessed over each microdialysis membrane. Dose-response curves were constructed and the EC50 was identified. For both SR and cutaneous vascular conductance (CVC), there were no significant differences in EC50 between sites receiving the same drug (P >0.05). However, the EC50 for CVC and SR at the MCh sites was significantly lower relative to the ACh sites. A second procedure was performed to confirm that differences in responses between drugs were due to differing cholinesterase sensitivities. Four microdialysis membranes were placed in dorsal forearm skin. Two sites were perfused with ACh and two sites with MCh. One of each of the ACh and MCh sites was co-perfused with 10 µM neostigmine (acetylcholinesterase inhibitor). Neostigmine at the ACh site induced a leftward shift (i.e. lower EC50) of the SR and CVC dose-response curves when compared to the site receiving only Ach (P <0.05). In contrast, neostigmine at the MCh site did not affect the EC50 for SR or CVC (P >0.05). These results suggest that MCh causes earlier elevations in SR and CVC relative to ACh due to differences in cholinesterase susceptibility between these drugs.
