L-arginine protects human heart cells from low-volume anoxia and reoxygenation.
Protective effects of L-arginine were evaluated in a human ventricular heart cell model of low-volume anoxia and reoxygenation independent of alternate cell types. Cell cultures were subjected to 90 min of low-volume anoxia and 30 min of reoxygenation. L-Arginine (0-5.0 mM) was administered during the preanoxic period or the reoxygenation phase. Nitric oxide (NO) production, NO synthase (NOS) activity, cGMP levels, and cellular injury were assessed. To evaluate the effects of the L-arginine on cell signaling, the effects of the NOS antagonist N(G)-nitro-L-arginine methyl ester, NO donor S-nitroso-N-acetyl-penicillamine, guanylate cyclase inhibitor methylene blue, cGMP analog 8-bromo-cGMP, and ATP-sensitive K+ channel antagonist glibenclamide were examined. Our data indicate that low-volume anoxia and reoxygenation increased NOS activity and facilitated the conversion of L-arginine to NO, which provided protection against cellular injury in a dose-dependent fashion. In addition, L-arginine cardioprotection was achieved by the activation of guanylate cyclase, leading to increased cGMP levels in human heart cells. This action involves a glibenclamide-sensitive, NO-cGMP-dependent pathway.
Shiono
Noritsugu
N
Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, M5G 2C4 Canada.
Rao
Vivek
V
Weisel
Richard D
RD
Kawasaki
Muneyasu
M
Li
Ren-Ke
RK
Mickle
Donald A G
DA
Fedak
Paul W M
PW
Tumiati
Laura C
LC
Ko
Lawrence
L
Verma
Subodh
S
D001120:Arginine / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects*; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010084:Oxidation-Reduction
D001120:Arginine; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III