Increased expression of gp91phox homologues of NAD(P)H oxidase in the aortic media during chronic hypertension: Involvement of the renin-angiotensin system

Takashi Akasaki, Yusuke Ohya, Junya Kuroda, Kimika Eto, Isao Abe, Hideki Sumimoto, Mitsuo Iida

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Although vascular cells express multiple members of the Nox family of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, including gp91phox, Nox1, and Nox4, the reasons for the different expressions and specific roles of these members in vascular injury in chronic hypertension have remained unclear. Thus, we quantified the mRNA expressions of these NAD(P)H oxidase components by real-time polymerase chain reaction and evaluated superoxide production and morphological changes in the aortas of 32-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar Kyoto rats (WKY). The aortic media of SHRSP had an approximately 2.5-fold greater level of Nox4 mRNA and an approximately 10-fold greater level of Nox1 mRNA than WKY. The mRNA expressions of gp91phox and p22phox in SHRSP and WKY were comparable. SHRSP were treated from 24 weeks of age for 8 weeks with either high or low doses of candesartan (4 mg/kg/day or 0.2 mglkg/day), or a combination of hydralazine (30 mg1kg1day) and hydrachlorathiazide (4.5 mg/kg/day). The high-dose candesartan or the hydralazine plus hydrochlorothiazide decreased the blood pressure of SHRSP to that of WKY, whereas the low-dose candesartan exerted no significant anti hypertensive action. Media thickening and fibrosis, as well as the increased production of superoxide in SHRSP, were nearly normalized with high-dose candesartan and partially corrected with low-dose candesartan or hydralazine plus hydrochlorothiazide. These changes by antihypertensive treatment paralleled the decrease in mRNA expression of Nox4 and Nox1. These results suggest that blood pressure and anglotensin II type 1 receptor activation are involved in the up-regulation of Nox1 and Nox4 expression, which could contribute to vascular injury during chronic hypertension.

Original languageEnglish
Pages (from-to)813-820
Number of pages8
JournalHypertension Research
Volume29
Issue number10
DOIs
Publication statusPublished - Oct 1 2006

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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