Inhibitory effect of recombinant iNOS gene expression on vasomotor function of canine basilar artery

Daihiko Eguchi, Livius V. D'Uscio, Chris Wambi, Deborah Weiler, Imre Kovesdi, Timothy O'Brien, Zvonimir S. Katusic

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The present study was designed to determine the effect of recombinant inducible nitric oxide (NO) synthase (iNOS) gene expression on vasomotor function in cerebral arteries. Isolated canine basilar arteries were exposed ex vivo (30 min at 37°C) to an adenoviral vector [107, 108, or 109 plaque-forming units (pfu)/ml] encoding either the iNOS gene or the β-galactosidase reporter gene. Twenty-four hours after transduction, Western blot analysis demonstrated expression of iNOS protein only in iNOS (109 pfu/ml)-transduced arteries. Immunohistochemical analysis localized iNOS expression predominantly in adventitia. Vascular reactivity of isolated basilar arteries was studied by isometric force recording. Concentration-response curves to UTP (10-9-10-3 M) and diethylaminodiazen-1-ium-1,2-dioate (10-10-10-5 M) were significantly shifted to the right in iNOS gene (109 pfu/ml)-transduced rings compared with control and β-galactosidase-transduced rings (P < 0.05, n = 5-6). Endothelium-dependent relaxation to bradykinin was significantly attenuated in iNOS-transduced rings (P < 0.001, n = 8). The basal level of cGMP and superoxide anion (O2-·) production were elevated in iNOS-transduced rings (P < 0.05, n = 7 for cGMP; P < 0.01, n = 6-9 for O2-· production). Our results suggest that expression of recombinant iNOS in cerebral arteries reduces vasomotor reactivity to both vasoconstrictor and vasodilator agonists. Attenuation of contractions is most likely due to functional antagonism between UTP and cGMP. Reduction of endothelium-dependent relaxation to bradykinin appears to be mediated in part by reduced reactivity of smooth muscle cells to NO.

Original languageEnglish (US)
Pages (from-to)H2560-H2566
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number6 52-6
DOIs
StatePublished - Dec 1 2002

Keywords

  • Adventitia
  • Bradykinin
  • Inducible nitric oxide synthase
  • Nitric oxide
  • Superoxide anion

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Inhibitory effect of recombinant iNOS gene expression on vasomotor function of canine basilar artery'. Together they form a unique fingerprint.

  • Cite this