Effects of NO donors and synthase agonists on endothelial cell uptake of L-Arg and superoxide production

Alison A. Ogonowski, Wayne H. Kaesemeyer, Liming Jin, Vadivel Ganapathy, Fredrick H. Leibach, R. William Caldwell

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

It is commonly believed that the activity of NO synthase (NOS) solely controls NO production from its substrates, L-Arg and O2. The Michaelis- Menten constant (K(m)) of NOS for L-Arg is in the micromolar range; cellular levels of L-Arg are much higher. However, evidence strongly suggests that cellular supply of L-Arg may become limiting and lead to reduced NO and increased superoxide anion (O2/-·) formation, promoting cardiovascular dysfunction. Uptake of L-Arg into cells occurs primarily (~85%) through the actions of a Na+-independent, carrier-mediated transporter (system y+). We have examined the effects of NOS agonists (substance P, bradykinin, and ACh) and NO donors (S-nitroso-N-acetyl-penicillamine and dipropylenetriamine NONOate) on transport of L-Arg into bovine aortic endothelial cells (BAEC). Our results demonstrate that NOS agonists increase y+ transporter activity. A rapidly acting NO donor initially increases L-Arg uptake; however, after longer exposure, L-Arg uptake is suppressed. Exposure of BAEC without L-Arg to substance P and a Ca2+ ionophore (A-23187) increased O2/-· formation, which was blocked with concurrent presence of L-Arg or the NOS antagonist N(ω)-nitro-L-arginine methyl ester. We conclude that factors including NO itself control y+ transport function and the production of NO and O2/-·.

Original languageEnglish (US)
Pages (from-to)C136-C143
JournalAmerican Journal of Physiology - Cell Physiology
Volume278
Issue number1 47-1
DOIs
StatePublished - Jan 1 2000

Keywords

  • Endothelial cells
  • L-arginine uptake
  • Nitric oxide
  • Transporter regulation
  • Vascular dysfunction

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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