Effects of recombinant eNOS gene expression on reactivity of small cerebral arteries

Masato Tsutsui, Hisashi Onoue, Yasuhiko Iida, Leslie Smith, Timothy O'Brien, Zvonimir S. Katusic

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Resistance arteries are an important target for vascular gene therapy because they play a key role in the regulation of tissue blood flow. The present study was designed to determine the effects of recombinant endothelial (e) nitric oxide synthase (NOS) gene expression on vasomotor reactivity of small brain stem arteries (internal diameter, 253 ± 2.5 μm). Arterial rings were exposed ex vivo to an adenoviral vector (109 and 1010 plaque-forming units/ml) encoding eNOS gene or β-galactosidase gene. Twenty-four hours after transduction, vascular function was examined by isometric force studies. Transgene expression was evident mainly in adventitia. In arteries with endothelium transduced with eNOS gene but not with control-β-galactosidase gene, relaxations to bradykinin and substance P were significantly augmented. Removal of endothelium abolished relaxations to bradykinin and substance P in control and β-galactosidase arteries. However, in endothelium-denuded arteries transduced with recombinant eNOS, bradykinin and substance P caused relaxations that were abolished in the presence of the NOS inhibitor N(G)-nitro-L-arginine methyl ester. In control arteries, endothelium removal augmented relaxations to the nitric oxide donors sodium nitroprusside and diethylamine NONOate. This augmentation was absent in eNOS gene-transduced arteries without endothelium. Our results suggest that, in small brain stem arteries, expression of recombinant eNOS increases biosynthesis of nitric oxide. Adventitia of small arteries is a good target for expression of recombinant eNOS. Genetically engineered adventitial cells may serve as a substitute source of nitric oxide in cerebral arteries with dysfunctional endothelium.

Original languageEnglish (US)
Pages (from-to)H420-H427
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume278
Issue number2 47-2
DOIs
StatePublished - Feb 2000

Keywords

  • Endothelial nitric oxide synthase
  • Microvessels
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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