Comparison of cholinergic vasodilator responses to acetylcholine and methacholine in the human forearm

Blood Pressure
T BruningP A Van Zwieten

Abstract

In order to study the contribution of the nitric oxide (NO)-pathway to cholinergic vasodilatation in the resistance vessels of the human forearm, we infused acetylcholine (ACh; 0.1 1000 ng/kg/min) or methacholine (MCh; 0.1 A 100 ng/kg/min) in the presence of saline, the NO-scavenger and guanylate cyclase inhibitor methylene blue (MB; 1000 ng/kg/min), or the NO-synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 30 micrograms/kg/min) into the brachial artery of normotensive volunteers (n = 32), using venous occlusion plethysmography. We calculated the plasma concentrations of the infused compounds to obtain EC50-values (-log mol/l). ACh and MCh both caused concentration-dependent vasodilatation (EC50-values of 6.43 +/- 0.05 and 7.24 +/- 0.08, respectively). MB (13 mumol/l) did not change basal forearm blood flow (FBF) when administered alone, but it markedly potentiated the vasodilator response to ACh, shifting the concentration-response curve (CRC) leftwards by 1.5 log-step (p < 0.001). MB did not affect MCh-induced vasodilatation. L-NMMA (1 mmol/l) alone caused dose-dependent vasoconstriction that was subject to tachyphylaxis. In addition, L-NMMA caused a steepening of the slopes of the CRCs of ACh, and MCh L-NMMA attenuated ...Continue Reading

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Citations

Jun 21, 2007·Endothelium : Journal of Endothelial Cell Research·M ErikssonL Lind
Nov 30, 2006·Clinical and Experimental Hypertension : CHE·George J MangosJohn J Kelly
Apr 8, 2004·Journal of Clinical Pharmacy and Therapeutics·A W E Weverling-RijnsburgerA E Meinders
Feb 24, 2006·Journal of Cardiovascular Pharmacology·Gary P Van GuilderChristopher A DeSouza
Feb 7, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Ahmed TawakolMark A Creager
Oct 11, 2001·Journal of Hypertension·B von zur MühlenL Lind
Feb 5, 2002·American Journal of Hypertension·Arvo HaenniHans Lithell
May 31, 2001·Clinical and Experimental Pharmacology & Physiology·B V MühlenL Lind
Jan 6, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Allison D FryerDavid A Jett
Jun 5, 2003·Journal of Hypertension·Leocadio Rodríguez-MañasCarlos F Sánchez-Ferrer

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