Abstract

To evaluate the potential role of the arterial oxidative stress in the pathogenesis of hypertension, the superoxide anion (O2.-) production in aortic ring and in cultured smooth muscle cells (SMC) from spontaneously hypertensive rats (SHR) was measured by lucigenin-enhanced chemiluminescence method.

The systolic blood pressure of 12-week old SHR was significantly higher than their controls WKY (p<0.05). The basal aortic ring O2.- generation was increased by 132% (p<0.05) in SHR compared to WKY (4.0±0.7 cpmx103/mg tissue). To determine the NADH oxidase activity, the NADH-stimulated O2.- generation was evaluated in aortic ring and found to be increased by 37% in SHR (p<0.05) compared to WKY (226±19 cpmx103/mg tissue). The relative contribution of NADH oxidase was determined by measuring the aortic basal O2.-production in presence of 100 mM DPI (Diphenylene iodonium chlorid), an NADH oxidase inhibitor. The diminution of the basal O2.- production was higher in SHR (-89.1%) than in WKY (-74.6%) suggesting that the relative contribution of this enzyme was enhanced in SHR. The basal and NADH-stimulated O2.- generation in cultured aortic SMC from SHR was also increased by 79% and 64% respectively compared to SMC from WKY (p<0.01). Although, at age of 6 weeks, there was no difference in blood pressure (BP) as well as in basal and in NADH-stimulated O2.- production between WKY and SHR rats, O2.- production and BP increased progressively and concomitantly in an age-dependant manner in 9 and 12 weeks SHR. Linear regression analysis indicated the existence of a positive correlation between the basal level of O2.- and the BP (r=0.683, p<0.001).

Our results demonstrated that the higher O2.- production in aortic ring and in cultured aortic SMC from SHR is mainly due to an enhanced activity of the NADH-oxidase and that this phenomenon is not secondary to the elevated blood pressure. The elevated arterial O2.- production seems to play a role in the development of hypertension in this experimental model since it increased in parallel with the blood pressure during grouth.

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