Vascular NADH/NADPH oxidase is involved in enhanced superoxide production in spontaneously hypertensive rats

This study was designed to test the hypothesis that stimulation of nicotina mide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH /NADPH) oxidase is involved in increased vascular superoxide anion (. O-2(- )) production in spontaneously hypertensive rats (SHR). The study was perfo rmed in 16-week-old and 30-week-old normotensive Wistar-Kyoto rats (WKY16 a nd WKY30, respectively) and in 16-week-old and 30-week-old SHR (SHR16 and S HR30, respectively). In addition, 16-week-old SHR were treated with oral ir besartan (average dose 20 mg/kg per day) for 14 weeks (SHR30-I). Aortic NAD H/NADPH oxidase activity was determined by use of chemiluminescence with lu cigenin. The expression of p22phox messenger RNA was assessed by competitiv e reverse transcription-polymerase chain reaction. Vascular responses to ac etylcholine were determined by isometric tension studies. Aortic wall struc ture was studied, determining the media thickness and the cross-sectional a rea by morphometric analysis. Whereas systolic blood pressure was significa ntly increased in the 2 groups of hypertensive animals compared with their normotensive controls, no differences were observed in systolic blood press ure between SHR30 and SHR16. No other differences in the parameters measure d were found between WKY16 and SHR16. In SHR30 compared with WKY30, we foun d significantly greater p22phox mRNA level, NADH/NADPH-driven . O-2(-) prod uction, media thickness, and cross-sectional area and an impaired vasodilat ion in response to acetylcholine. Treated SHR had similar NADH/NADPH oxidas e activity and p22phox expression as the WKY,, group. The vascular function al and morphological parameters were improved in SHR50-I. These findings su ggest that an association exists between p22phox gene overexpression and NA DH/NADPH overactivity in the aortas of adult SHR. Enhanced NADH/NADPH oxida se-dependent . O-2(-) production may contribute to endothelial dysfunction and vascular hypertrophy in this genetic model of hypertension.