Arginase inhibition increases nitric oxide production in bovine pulmonary arterial endothelial cells

LG Chicoine, ML Paffett, TL Young… - American Journal of …, 2004 - journals.physiology.org
LG Chicoine, ML Paffett, TL Young, LD Nelin
American Journal of Physiology-Lung Cellular and Molecular …, 2004journals.physiology.org
Nitric oxide (NO) is produced by NO synthase (NOS) from l-arginine (l-Arg). Alternatively, l-
Arg can be metabolized by arginase to produce l-ornithine and urea. Arginase (AR) exists in
two isoforms, ARI and ARII. We hypothesized that inhibiting AR with l-valine (l-Val) would
increase NO production in bovine pulmonary arterial endothelial cells (bPAEC). bPAEC
were grown to confluence in either regular medium (EGM; control) or EGM with
lipopolysaccharide and tumor necrosis factor-α (L/T) added. Treatment of bPAEC with L/T …
Nitric oxide (NO) is produced by NO synthase (NOS) from l-arginine (l-Arg). Alternatively, l-Arg can be metabolized by arginase to produce l-ornithine and urea. Arginase (AR) exists in two isoforms, ARI and ARII. We hypothesized that inhibiting AR with l-valine (l-Val) would increase NO production in bovine pulmonary arterial endothelial cells (bPAEC). bPAEC were grown to confluence in either regular medium (EGM; control) or EGM with lipopolysaccharide and tumor necrosis factor-α (L/T) added. Treatment of bPAEC with L/T resulted in greater ARI protein expression and ARII mRNA expression than in control bPAEC. Addition of l-Val to the medium led to a concentration-dependent decrease in urea production and a concentration-dependent increase in NO production in both control and L/T-treated bPAEC. In a second set of experiments, control and L/T bPAEC were grown in EGM, EGM with 30 mM l-Val, EGM with 10 mM l-Arg, or EGM with both 10 mM l-Arg and 30 mM l-Val. In both control and L/T bPAEC, treatment with l-Val decreased urea production and increased NO production. Treatment with l-Arg increased both urea and NO production. The addition of the combination l-Arg and l-Val decreased urea production compared with the addition of l-Arg alone and increased NO production compared with l-Val alone. These data suggest that competition for intracellular l-Arg by AR may be involved in the regulation of NOS activity in control bPAEC and in response to L/T treatment.
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