Adventitia-dependent relaxations of canine basilar arteries transduced with recombinant eNOS gene

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

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

We recently reported that expression of recombinant endothelial nitric oxide (NO) synthase (eNOS) gene in adventitial fibroblasts restores NO formation in canine cerebral arteries without endothelium in response to bradykinin ex vivo and in vivo. The present study was designed to further characterize the stimuli that can activate recombinant eNOS enzyme expressed in the adventitia of cerebral arteries. To stimulate recombinant eNOS, we used serum (0.1-10%), substance P (10-11-3 X 10-9 M), and ANG II (10- 7-10-5 M) because they increase intracellular calcium concentrations in fibroblasts. Endothelium-denuded segments of canine basilar arteries were incubated with an adenoviral vector encoding β-galactosidase gene or eNOS gene for 30 min at 37°C. After 24 h, vasomotor activity and cGMP formation in eNOS or β-galactosidase arteries were examined by isometric force recording and by radioimmunoassay, respectively. In control arteries and β- galactosidase gene-transduced arteries, serum caused concentration-dependent contractions, whereas in recombinant eNOS gene-transduced arteries, serum produced concentration-dependent relaxations. Substance P and ANG II had no effect on vascular tone in control and β-galactosidase arteries but caused concentration-dependent relaxations as well as a significant increase in cGMP levels in eNOS arteries. These relaxations were blocked by the NOS inhibitor N(G)-nitro-L-arginine methyl ester. Chemical treatment or mechanical inactivation of adventitial function significantly attenuated substance P- induced relaxations and ANG II-induced relaxations. These findings demonstrate that serum, substance P, and ANG II cause adventitia-dependent relaxations in cerebral arteries expressing the recombinant eNOS gene. This mechanism of vasodilatation may have beneficial effects in the prevention and treatment of vascular disorders characterized by the diminished bioavailability of NO, such as cerebral vasospasm.

Original languageEnglish (US)
Pages (from-to)H1846-H1852
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume276
Issue number6 45-6
DOIs
StatePublished - Jun 1999

Keywords

  • Angiotensin II
  • Bradykinin
  • Cerebral arteries
  • Endothelial nitric oxide synthase
  • Gene transfer
  • Nitric oxide
  • Serum

ASJC Scopus subject areas

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

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