Adventitial expression of recombinant endothelial nitric oxide synthase gene reverses vasoconstrictor effect of endothelin-1

H. Onoue, M. Tsutsui, L. Smith, T. O'Brien, Z. S. Katusic

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The present study was designed to determine the effect of recombinant endothelial nitric oxide synthase (eNOS) gene expression on reactivity of canine basilar arteries to endothelin-1 (ET-1). The arteries were exposed (30 min at 37°C ex vivo) to adenoviral vectors encoding eNOS gene (AdCMVeNOS) or β-galactosidase reporter gene (AdCMVβ-Gal). Twenty-four hours following transduction, transgene expression was evident mainly in the vascular adventitia. During contractions to uridine 5′-triphosphate (UTP), ET-1 (10-10 to 3 x 10-9M) caused further increase in tension in control and AdCMVβ-Gal-transduced arteries. In contrast, ET-1 caused concentration-dependent relaxations of AdCMVeNOS-transduced arteries. The relaxations to ET-1 were endothelium-independent. They were abolished by NG-nitro-L-arginine methyl ester or by chemical treatment of the adventitia with paraformaldehyde prior to gene transfer. ET-1 (10-9M) significantly increased intracellular cyclic GMP levels only in arteries expressing recombinant eNOS gene. The relaxations to ET-1 in AdCMVeNOS-transduced arteries were strongly reduced by BQ-123, an ETA receptor antagonist, but were not affected by BQ-788, an ETB receptor antagonist. These results demonstrate that genetically modified adventitia of cerebral arteries can produce nitric oxide in response to ET-1 via activation of ETA receptors.

Original languageEnglish (US)
Pages (from-to)A639
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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