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Agmatine‐mediated rat mesenteric artery relaxation via NO synthesis
Author(s) -
Gadkari Tushar,
Acosta Zenith,
Tsoukias Nikolaos,
Joshi Mahesh S
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.984.23
Subject(s) - agmatine , mesenteric arteries , nitric oxide , nitric oxide synthase , arginine , chemistry , intracellular , superior mesenteric artery , endocrinology , biophysics , artery , medicine , biochemistry , biology , amino acid
Aim To determine membrane receptor‐dependent or independent mechanisms of agmatine (decarboxylated arginine) relaxation of rat mesenteric arteries. Background In spite of excess levels of intracellular L‐arginine, exogenous L‐arginine still activates cellular synthesis of nitric oxide (NO) in a phenomenon called “arginine paradox”. Our previously published data (PNAS, 104, 9982, 2007) show that L‐arginine or agmatine may be initiating the NO synthesis via receptor binding and release of intracellular Ca +2 in endothelial cells. Here we have tested the same mechanism in isolated rat mesenteric arteries. Methods The individual 2 nd order mesenteric arteriolar segments from rats (250–300 g male, Sprague‐Dawley) were cannulated at both ends in a vessel chamber that was continuously perfused intraluminally and pre‐constricted with norepinephrine (2 μM) in modified Krebs buffer at 37°C. For internal diameter measurements, the vessel chamber was mounted on the stage of a microscope fitted with a video camera leading to video caliper. Mounted vessels were allowed to stabilize for 60 min before initiating experiment. Results The data show that agmatine completely relaxed the vessel with an EC 50 of 58.75 ± 12.1 μM (n=4) and this relaxation could be significantly inhibited with nitric oxide synthase inhibitor, L‐NAME (0.5 mM) with EC 50 of 315 μM (n=1). Conclusion Agmatine dose‐dependently relaxed the rat mesenteric artery and NO mediated the relaxation process. This work was supported in part by NIH grant SC1HL095101