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. 1993 Oct;110(2):736–738. doi: 10.1111/j.1476-5381.1993.tb13873.x

Differential inhibition by NG-monomethyl-L-arginine of vasodilator effects of acetylcholine and methacholine in human forearm vasculature.

P J Chowienczyk 1, J R Cockcroft 1, J M Ritter 1
PMCID: PMC2175929  PMID: 8242245

Abstract

1. 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. 2. 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. 3. Co-infusion of L-NMMA (4 mumol 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). 4. 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. 5. Co-infusion of L-NMMA (4 mumol 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 mumol min-1) with methacholine (1.5 nmol min-1) did not significantly inhibit the vasodilator response (n = 7). 6. These results suggest that, in human forearm vasculature, methacholine acts predominantly through mechanisms other than the L-arginine/nitric oxide pathway.

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Selected References

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  1. Brayden J. E., Bevan J. A. Neurogenic muscarinic vasodilation in the cat. An example of endothelial cell-independent cholinergic relaxation. Circ Res. 1985 Feb;56(2):205–211. doi: 10.1161/01.res.56.2.205. [DOI] [PubMed] [Google Scholar]
  2. Chen G., Suzuki H., Weston A. H. Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels. Br J Pharmacol. 1988 Dec;95(4):1165–1174. doi: 10.1111/j.1476-5381.1988.tb11752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chowienczyk P. J., Watts G. F., Cockcroft J. R., Ritter J. M. Impaired endothelium-dependent vasodilation of forearm resistance vessels in hypercholesterolaemia. Lancet. 1992 Dec 12;340(8833):1430–1432. doi: 10.1016/0140-6736(92)92621-l. [DOI] [PubMed] [Google Scholar]
  4. Creager M. A., Cooke J. P., Mendelsohn M. E., Gallagher S. J., Coleman S. M., Loscalzo J., Dzau V. J. Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. J Clin Invest. 1990 Jul;86(1):228–234. doi: 10.1172/JCI114688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Creager M. A., Gallagher S. J., Girerd X. J., Coleman S. M., Dzau V. J., Cooke J. P. L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. J Clin Invest. 1992 Oct;90(4):1248–1253. doi: 10.1172/JCI115987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DUFF F., GREENFIELD A. D., SHEPHERD J. T., THOMPSON I. D. A quantitative study of the response to acetylcholine and histamine of the blood vessels of the human hand and forearm. J Physiol. 1953 Apr 28;120(1-2):160–170. doi: 10.1113/jphysiol.1953.sp004883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dauphin F., Hamel E. Identification of multiple muscarinic binding site subtypes in cat and human cerebral vasculature. J Pharmacol Exp Ther. 1992 Feb;260(2):660–667. [PubMed] [Google Scholar]
  8. Feletou M., Vanhoutte P. M. Endothelium-dependent hyperpolarization of canine coronary smooth muscle. Br J Pharmacol. 1988 Mar;93(3):515–524. doi: 10.1111/j.1476-5381.1988.tb10306.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  10. Hokanson D. E., Sumner D. S., Strandness D. E., Jr An electrically calibrated plethysmograph for direct measurement of limb blood flow. IEEE Trans Biomed Eng. 1975 Jan;22(1):25–29. doi: 10.1109/tbme.1975.324535. [DOI] [PubMed] [Google Scholar]
  11. Jaiswal N., Lambrecht G., Mutschler E., Tacke R., Malik K. U. Pharmacological characterization of the vascular muscarinic receptors mediating relaxation and contraction in rabbit aorta. J Pharmacol Exp Ther. 1991 Sep;258(3):842–850. [PubMed] [Google Scholar]
  12. Liao J. K., Bettmann M. A., Sandor T., Tucker J. I., Coleman S. M., Creager M. A. Differential impairment of vasodilator responsiveness of peripheral resistance and conduit vessels in humans with atherosclerosis. Circ Res. 1991 Apr;68(4):1027–1034. doi: 10.1161/01.res.68.4.1027. [DOI] [PubMed] [Google Scholar]
  13. Linder L., Kiowski W., Bühler F. R., Lüscher T. F. Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. Circulation. 1990 Jun;81(6):1762–1767. doi: 10.1161/01.cir.81.6.1762. [DOI] [PubMed] [Google Scholar]
  14. Nagao T., Illiano S., Vanhoutte P. M. Heterogeneous distribution of endothelium-dependent relaxations resistant to NG-nitro-L-arginine in rats. Am J Physiol. 1992 Oct;263(4 Pt 2):H1090–H1094. doi: 10.1152/ajpheart.1992.263.4.H1090. [DOI] [PubMed] [Google Scholar]
  15. Nagao T., Vanhoutte P. M. Hyperpolarization as a mechanism for endothelium-dependent relaxations in the porcine coronary artery. J Physiol. 1992 Jan;445:355–367. doi: 10.1113/jphysiol.1992.sp018928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Neild T. O., Shen K. Z., Surprenant A. Vasodilatation of arterioles by acetylcholine released from single neurones in the guinea-pig submucosal plexus. J Physiol. 1990 Jan;420:247–265. doi: 10.1113/jphysiol.1990.sp017910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rubanyi G. M., McKinney M., Vanhoutte P. M. Biphasic release of endothelium-derived relaxing factor(s) by acetylcholine from perfused canine femoral arteries. Characterization of muscarinic receptors. J Pharmacol Exp Ther. 1987 Mar;240(3):802–808. [PubMed] [Google Scholar]
  18. Vallance P., Collier J., Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet. 1989 Oct 28;2(8670):997–1000. doi: 10.1016/s0140-6736(89)91013-1. [DOI] [PubMed] [Google Scholar]
  19. WHITNEY R. J. The measurement of volume changes in human limbs. J Physiol. 1953 Jul;121(1):1–27. doi: 10.1113/jphysiol.1953.sp004926. [DOI] [PMC free article] [PubMed] [Google Scholar]

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