QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.104422v1 318/3/1044    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, J. Articles by Zhang, C. Search for Related Content PubMed PubMed Citation Articles by Yang, J. Articles by Zhang, C.

CARDIOVASCULAR

L-Arginine Chlorination Results in the Formation of a Nonselective Nitric-Oxide Synthase Inhibitor

Vascular Biology Center and Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee (J.Y., R.J, Y.C., L.K.J., C.Z.); and Department of Surgery, Emory University School of Medicine, Atlanta, Georgia (J.-Z.S.)

Reduced nitric oxide (NO) bioavailability and impaired vascular function are the key pathological characteristics of inflammatory diseases such as atherosclerosis. We have recently found that leukocyte-derived hypochlorous acid is able to react with the nitric-oxide synthase (NOS) substrate L-arginine to produce chlorinated L-arginine (cl-L-Arg). Interestingly, cl-L-Arg potently inhibits the formation of NO metabolites in cultured endothelial cells. It is unknown whether cl-L-Arg has a direct inhibitory effect on endothelial NOS (eNOS). In addition, the effect of cl-L-Arg on the other NOS isoforms, neuronal NOS (nNOS) and inducible NOS (iNOS), is also unknown. Therefore, we designed the current study to test the effects of cl-L-Arg on eNOS, nNOS, and iNOS. Using recombinant NOS, we found that cl-L-Arg had a direct inhibitory effect on the activity of NOS. The effect of cl-L-Arg on NOS activity is nonselective, as all three NOS isoforms were inhibited with a similar IC₅₀. We further determined the effect of cl-L-Arg on the three NOS isoforms at the tissue level. The results demonstrated that cl-L-Arg potently inhibited all three NOS isoform-mediated vessel reactivities, as well as the NOS signaling molecule cGMP. Cl-L-Arg might serve as a novel endogenous NOS inhibitor and an important mediator for vascular dysfunction under inflammatory conditions such as atherosclerosis. Blocking cl-L-Arg formation may be a new therapeutic approach to cardiovascular diseases.

Address correspondence to: Dr. Chunxiang Zhang, Vascular Injury Laboratory, Vascular Biology Center and Department of Surgery, University of Tennessee Health Science Center, 956 Court Ave., Coleman Bldg., H300, Memphis, TN 38163. E-mail: czhang{at}utmem.edu

This article has been cited by other articles:

				T. Radovits, J. Zotkina, L.-N. Lin, T. Bomicke, R. Arif, D. Gero, E. M. Horvath, M. Karck, C. Szabo, and G. Szabo Poly(ADP-Ribose) Polymerase Inhibition Improves Endothelial Dysfunction Induced by Hypochlorite Experimental Biology and Medicine, October 1, 2007; 232(9): 1204 - 1212. [Abstract] [Full Text] [PDF]