p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats

Toshiki Fukui, Nobukazu Ishizaka, Sanjay Rajagopalan, Jørn Bech Laursen, Quinn Capers IV, W. Robert Taylor, David G. Harrison, Hector De Leon, Josiah N. Wilcox, Kathy K. Griendling

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies suggest that superoxide production by the NADPH/NADH oxidase may be involved in smooth muscle cell growth and the pathogenesis of hypertension. We previously showed that angiotensin II (Ang II) activates a p22phox based NADPH/NADH oxidase in cultured rat vascular' smooth muscle cells and in animals made hypertensive by infusion of Ang II. To investigate the mechanism responsible for this in creased oxidase activity, we examined p22phox mRNA expression in rats made hypertensive by implanting an osmotic minipump that delivered Ang II (0.7 mg/kg per day). Blood pressure began to increase 3 days after the start of Ang II infusion and remained elevated for up to 14 days. Expression of p22phox mRNA in aorta was also increased after 3 days and reached a maximum increase of 338±41% by 5 days after pump implantation compared with the value after sham operation. This increase in mRNA expression was accompanied by an increase in the content of the corresponding cytochrome (twofold) and NADPH oxidase activity (179 ± 11% of that in sham operated rats 5 days after pump implantation). Treatment with the antihypertensive agents losartan (25 mg/kg per day) or hydralazine (15 mg/kg per day) inhibited this upregulation of mRNA levels and activity. Furthermore, infusion of recombinant heparin-binding superoxide dismutase decreased both blood pressure and p22phox mRNA expression. In situ hybridization of aortic tissue showed that p22phox mRNA was expressed in medial smooth muscle as well as in the adventitia. These findings suggest that Ang II-induced hypertension activates the NADPH/NADH oxidase system by upregulating mRNA levels of one or several components of this oxidase system, including the p22phox, and that the NADPH/NADH oxidase system is associated with the pathology of hypertension in vivo.

Original languageEnglish (US)
Pages (from-to)45-51
Number of pages7
JournalCirculation research
Volume80
Issue number1
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • angiotensin II
  • hypertension
  • muscle, smooth, vascular
  • NADPH oxidase
  • p22phox

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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