Differential inhibition by NG‐monomethyl‐l‐arginine of vasodilator effects of acetylcholine and methacholine in human forearm vasculature

P. J. Chowienczyk*, J. R. Cockcroft, J. M. Ritter

*Corresponding author for this work

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

We compared the effects of NG‐monomethyl‐l‐arginine (l‐NMMA), an NO synthase inhibitor, on vasodilatation produced by acetylcholine and methacholine in human forearm vasculature. Acetylcholine (83 nmol min−1) infused into the brachial artery of 8 healthy volunteers caused a submaximal increase in forearm blood flow, measured by venous occlusion plethysmography, from 3.3 ± 0.5 (mean ± s.e.mean) to 13.3 ± 1.7 ml min−1 100 ml−1. Co‐infusion of l‐NMMA (4 μmol min−1) with acetylcholine (83 nmol min−1) over 6 min resulted in a 58% ± 12% fall in the response to acetylcholine whereas during co‐infusion of saline over the same time period in the same subjects (n = 8) on a different day the response to acetylcholine fell by only 9% ± 17% (P < 0.01). Methacholine (1.5 and 15 nmol min−1) increased forearm blood flow from 2.5 ± 0.4 to 5.9 ± 0.9 and from 3.2 ± 0.4 to 17.0 ± 1.9 ml min−1 100 ml−1 respectively. Co‐infusion of l‐NMMA (4 μmol min−1) had no significant effect on the response to methacholine (1.5 or 15 nmol min−1) when compared with saline control (n = 8). Co‐infusion of a higher dose of l‐NMMA (8 μmol min−1) with methacholine (1.5 nmol min−1) did not significantly inhibit the vasodilator response (n = 7). These results suggest that, in human forearm vasculature, methacholine acts predominantly through mechanisms other than the l‐arginine/nitric oxide pathway. 1993 British Pharmacological Society

Original languageEnglish
Pages (from-to)736-738
Number of pages3
JournalBritish Journal of Pharmacology
Volume110
Issue number2
DOIs
Publication statusPublished - 1993

Keywords

  • acetylcholine
  • Endothelium
  • human forearm vasculature
  • methacholine
  • muscarinic receptors
  • N‐monomethyl‐l‐arginine
  • nitric oxide

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