PMID- 16155089
OWN - NLM
STAT- MEDLINE
DCOM- 20060209
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 290
IP  - 2
DP  - 2006 Feb
TI  - Gene transfer with inducible nitric oxide synthase decreases production of urea 
      by arginase in pulmonary arterial endothelial cells.
PG  - L298-306
AB  - Nitric oxide (NO) is a vasodilator produced from L-arginine (L-Arg) by NO 
      synthase (NOS). Gene therapy for hypertensive disorders has been proposed using 
      the inducible isoform of NOS (iNOS). L-Arg also can be metabolized to urea and 
      L-ornithine (L-Orn) by arginase, and L-Orn can be metabolized to proline and/or 
      polyamines, which are vital for cellular proliferation. To determine the effect 
      of iNOS gene transfer on arginase, we transfected bovine pulmonary arterial 
      endothelial cells (bPAEC) with an adenoviral vector containing the gene for iNOS 
      (AdiNOS). As expected, NO production in AdiNOS bPAEC was substantially greater 
      than in control bPAEC. Although urea production was significantly less in the 
      AdiNOS bPAEC than in the control bPAEC, despite similar levels of arginase I 
      protein, AdiNOS transfection of bPAEC had no effect on the uptake of L-Arg. 
      Inhibiting NO production with Nomega-nitro-L-arginine methyl ester increased urea 
      production, and inhibiting urea production with L-valine increased nitrite 
      production, in AdiNOS bPAEC. The addition of L-Arg to the medium increased urea 
      production by AdiNOS bPAEC in a concentration-dependent manner. Thus, in these 
      iNOS-transfected bPAEC, the transfected iNOS and native arginase compete for a 
      common intracellular pool of L-Arg. This competition for substrate resulted in 
      impaired proliferation in the AdiNOS-transfected bPAEC. These findings suggest 
      that the use of iNOS gene therapy for pulmonary hypertensive disorders may not 
      only be beneficial through NO-mediated pulmonary vasodilation but also may 
      decrease vascular remodeling by limiting L-Orn production by native arginase.
FAU - Stanley, Kate P
AU  - Stanley KP
AD  - Vascular Physiology Group, Department of Internal Medicine, University of New 
      Mexico Health Sciences Center, Albuquerque, NM and Center for Developmental 
      Pharmacology and Toxicology, Columbus Children's Research Institute, Columbus, OH 
      43205, USA.
FAU - Chicoine, Louis G
AU  - Chicoine LG
FAU - Young, Tamara L
AU  - Young TL
FAU - Reber, Kristina M
AU  - Reber KM
FAU - Lyons, C Richard
AU  - Lyons CR
FAU - Liu, Yusen
AU  - Liu Y
FAU - Nelin, Leif D
AU  - Nelin LD
LA  - eng
GR  - HL-04050/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20050909
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 8W8T17847W (Urea)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 3.5.3.1 (Arginase)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Arginase/antagonists & inhibitors/*metabolism
MH  - Arginine/pharmacology
MH  - Cattle
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Endothelium, Vascular/*metabolism
MH  - Gene Expression Profiling
MH  - *Gene Transfer Techniques
MH  - Genetic Vectors
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/biosynthesis/*genetics
MH  - Nitric Oxide Synthase Type III/biosynthesis
MH  - Pulmonary Artery/*cytology
MH  - Urea/*metabolism
EDAT- 2005/09/13 09:00
MHDA- 2006/02/10 09:00
CRDT- 2005/09/13 09:00
PHST- 2005/09/13 09:00 [pubmed]
PHST- 2006/02/10 09:00 [medline]
PHST- 2005/09/13 09:00 [entrez]
AID - 00140.2005 [pii]
AID - 10.1152/ajplung.00140.2005 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2006 Feb;290(2):L298-306. doi: 
      10.1152/ajplung.00140.2005. Epub 2005 Sep 9.