This Article Full Text Full Text (PDF) All Versions of this Article: 36/1/158    most recent 01.STR.0000150489.47080.67v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sorenson, J. Articles by Katusic, Z. S. Search for Related Content PubMed PubMed Citation Articles by Sorenson, J. Articles by Katusic, Z. S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-ASPARTIC ACID L-SERINE Related Collections Endothelium/vascular type/nitric oxide

(Stroke. 2005;36:158.)
© 2005 American Heart Association, Inc.

Research Reports

Expression and Function of Recombinant S1179D Endothelial NO Synthase in Human Pial Arteries

Joseph Sorenson, BS; Anantha Vijay R. Santhanam, PhD; Leslie A. Smith; Masahiko Akiyama, MD; William C. Sessa, PhD Zvonimir S. Katusic, MD, PhD

From the Departments of Anesthesiology and Molecular Pharmacology and Experimental Therapeutics (J.S., A.V.R.S., L.A.S., M.A., Z.S.K.), Mayo Clinic, Rochester, Minn; and Department of Pharmacology and Molecular Cardiobiology Program (W.C.S.), Yale University School of Medicine, New Haven, Conn.

Correspondence to Dr Zvonimir S. Katusic, Department of Anesthesiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail katusic.zvonimir{at}mayo.edu

Background and Purpose— Mutation of serine 1179 to aspartate on the endothelial NO synthase (eNOS) increases NO production in the absence of stimulation by agonists. The present study was designed to determine the effect of recombinant S1179DeNOS gene expression on the vasomotor function of human pial arteries.

Methods— Pial arteries were isolated from 28 patients undergoing temporal lobectomy for intractable seizures. Adenoviral vectors (10¹⁰ pfu/mL) encoding ß-galactosidase (AdCMVLacZ) or S1179DeNOS (AdCMVS1179DeNOS) were used for ex vivo gene transfer, and vasomotor function was evaluated in control and transduced arteries.

Results— Contractions to cumulative additions of U46619 were not affected by expression of LacZ or S1179DeNOS. Endothelium-dependent relaxations to bradykinin or endothelium-independent relaxations to Diethylaminodiazen-1-ium-1,2-dioate were significantly reduced in arteries expressing S1179DeNOS. A superoxide dismutase mimetic, manganese (III) tetrakis (4-benzoic acid) porphyrin chloride, failed to improve the reduced relaxations to bradykinin. The levels of cGMP were significantly elevated in arteries expressing S1179DeNOS.

Conclusions— Our results support the concept that high local production of NO in pial arterial wall causes adaptive reduction of vasodilator reactivity to NO.

Key Words: free radicals • gene therapy • nitric oxide

This article has been cited by other articles:

				M. Herrera, N. J. Hong, P. A. Ortiz, and J. L. Garvin Endothelin-1 Inhibits Thick Ascending Limb Transport via Akt-stimulated Nitric Oxide Production J. Biol. Chem., January 16, 2009; 284(3): 1454 - 1460. [Abstract] [Full Text] [PDF]

				F. M. Faraci Editorial Comment: eNOS: Can We Exploit the Good? Stroke, January 1, 2005; 36(1): 160 - 161. [Full Text] [PDF]