Expression and function of recombinant S1179D endothelial NO synthase in human pial arteries

Joseph Sorenson, A. V R Santhanam, Leslie A. Smith, Masahiko Akiyama, William C. Sessa, Zvonimir S Katusic

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 (10 10 pfu/mL) encoding β-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.

Original languageEnglish (US)
Pages (from-to)158-160
Number of pages3
JournalStroke
Volume36
Issue number1
DOIs
StatePublished - Jan 2005

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Nitric Oxide Synthase
Arteries
Bradykinin
Endothelium
Galactosidases
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Vasodilator Agents
Aspartic Acid
Serine
Superoxide Dismutase
Chlorides
Seizures
Gene Expression
Mutation
Genes

Keywords

  • Free radicals
  • Gene therapy
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Expression and function of recombinant S1179D endothelial NO synthase in human pial arteries. / Sorenson, Joseph; Santhanam, A. V R; Smith, Leslie A.; Akiyama, Masahiko; Sessa, William C.; Katusic, Zvonimir S.

In: Stroke, Vol. 36, No. 1, 01.2005, p. 158-160.

Research output: Contribution to journalArticle

Sorenson, Joseph ; Santhanam, A. V R ; Smith, Leslie A. ; Akiyama, Masahiko ; Sessa, William C. ; Katusic, Zvonimir S. / Expression and function of recombinant S1179D endothelial NO synthase in human pial arteries. In: Stroke. 2005 ; Vol. 36, No. 1. pp. 158-160.
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