Effect of an arginine analogue on acetylcholine-induced coronary microvascular dilatation in dogs

T. Komaru, K. G. Lamping, C. L. Eastham, D. G. Harrison, M. L. Marcus, K. C. Dellsperger

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63 Scopus citations


The purpose of this study was to elucidate the contribution of endothelium-derived relaxing factor (EDRF) derived from arginine to acetylcholine (ACh)-induced coronary arteriolar vasodilatation in vivo. Experiments were performed in 62 open-chest anesthetized dogs. Internal diameters of small arterioles (<120 μm) and large arterioles (>120 μm) were measured using an intravital microscope and stroboscopic epiillumination synchronized to the cardiac cycle. Topically administered N(G)-monomethyl-L-arginine (L-NMMA, 3 x 10-4 M) constricted small arterioles (-10.7 ± 3.1% from control diameter, P < 0.05), but L-NMMA did not produce vasoconstriction in large arterioles. ACh, in the absence of L-NMMA, caused a dose-dependent vasodilatation in both small and large arterioles. In large arterioles, L-NMMA completely abolished the ACh-induced vasodilatation (10-5 M topical ACh: from 13.3 ± 3.0 to -2.0 ± 1.5%, P < 0.05; 10-4 M ACh: from 20.9 ± 3.9 to -3.0 ± 1.9%, P < 0.01). In small arterioles, L-NMMA only partially inhibited the vasodilatation (10-5 M ACh: from 35.4 ± 4.0 to 19.0 ± 2.7%, P < 0.05; 10-4 M ACh: from 42.5 ± 4.8 to 22.6 ± 3.1%, P < 0.05). L-Arginine (10-3 M topically) reversed L-NMMA inhibition of ACh-induced vasodilatation. Persistent dilatation of small arterioles also occurred when N(G)-nitro-L-arginine rather than L-NMMA was administered. Neither K+ channel blockers [glibenclamide (10-5 M) and tetraethylammonium (3 x 10-2 M)] nor indomethacin (5 x 10-5 M) had an additional inhibitory effect on ACh-induced vasodilatation in the presence of L-arginine analogue. These data suggest that EDRF derived from arginine modulates basal tone in small arterioles but that arginine is unlikely to be the only source of factors that modulate ACh-induced vasodilatation in these vessels. In contrast, a nitrosyl compound derived from arginine exclusively accounts for ACh-induced vasodilatation in large arterioles.

Original languageEnglish (US)
Pages (from-to)H2001-H2007
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6 30-6
StatePublished - 1991
Externally publishedYes


  • Coronary arterioles
  • Endothelium-derived relaxing factor
  • Glibenclamide
  • Indomethacin
  • Intravital microscopy
  • L-arginine
  • N(G)-monomethyl-L-arginine
  • N(G)-nitro-L-arginine
  • Tetraethylammonium

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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