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, Robert William Caldwell

Research output: Contribution to journalArticle

60 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Cell Physiology
Volume278
Issue number1 47-1
StatePublished - Feb 29 2000

Fingerprint

Nitric Oxide Synthase
Superoxides
Endothelial Cells
Substance P
Amino Acid Transport System y+
Penicillamine
Ionophores
Calcimycin
Bradykinin

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Effects of NO donors and synthase agonists on endothelial cell uptake of L-Arg and superoxide production. / Ogonowski, Alison A.; Kaesemeyer, Wayne H.; Jin, Liming; Ganapathy, Vadivel; Leibach, Fredrick H.; Caldwell, Robert William.

In: American Journal of Physiology - Cell Physiology, Vol. 278, No. 1 47-1, 29.02.2000.

Research output: Contribution to journalArticle

Ogonowski, Alison A. ; Kaesemeyer, Wayne H. ; Jin, Liming ; Ganapathy, Vadivel ; Leibach, Fredrick H. ; Caldwell, Robert William. / Effects of NO donors and synthase agonists on endothelial cell uptake of L-Arg and superoxide production. In: American Journal of Physiology - Cell Physiology. 2000 ; Vol. 278, No. 1 47-1.
@article{fda70f2bad4c4fe386f35832ba292ead,
title = "Effects of NO donors and synthase agonists on endothelial cell uptake of L-Arg and superoxide production",
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/-·.",
keywords = "Endothelial cells, L-arginine uptake, Nitric oxide, Transporter regulation, Vascular dysfunction",
author = "Ogonowski, {Alison A.} and Kaesemeyer, {Wayne H.} and Liming Jin and Vadivel Ganapathy and Leibach, {Fredrick H.} and Caldwell, {Robert William}",
year = "2000",
month = "2",
day = "29",
language = "English (US)",
volume = "278",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1 47-1",

}

TY - JOUR

T1 - Effects of NO donors and synthase agonists on endothelial cell uptake of L-Arg and superoxide production

AU - Ogonowski, Alison A.

AU - Kaesemeyer, Wayne H.

AU - Jin, Liming

AU - Ganapathy, Vadivel

AU - Leibach, Fredrick H.

AU - Caldwell, Robert William

PY - 2000/2/29

Y1 - 2000/2/29

N2 - 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/-·.

AB - 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/-·.

KW - Endothelial cells

KW - L-arginine uptake

KW - Nitric oxide

KW - Transporter regulation

KW - Vascular dysfunction

UR - http://www.scopus.com/inward/record.url?scp=0033976693&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033976693&partnerID=8YFLogxK

M3 - Article

C2 - 10644521

AN - SCOPUS:0033976693

VL - 278

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 1 47-1

ER -