Prenatal high-salt diet impaired vasodilatation with reprogrammed renin–angiotensin system in offspring rats

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Aims:High-salt diet is linked to hypertension, and prenatal high-salt diet increases the risk of cardiovascular diseases in the offspring. The present study investigated whether and how prenatal high-salt diet influenced nitric oxide-mediated vasodilatation in the offspring.Methods and results:Pregnant rats were fed either normal-salt (1% sodium chloride) or high-salt (8% sodium chloride) diet during gestation. Experiments were conducted in 5-month-old male offspring. Sodium nitroprusside (SNP, nitric oxide donor)-induced hypotensive responses (in vivo) and vascular dilatation (in vitro) was significantly attenuated (Emax: 84 ± 2 vs. 51 ± 2, high-salt vs. control, P < 0.001) in the high-salt offspring, indicating reduced vascular relaxations. Pretreatment with Tempol (reactive oxygen species scavenger) alleviated this attenuation. The high-salt offspring showed an increased level of oxidative stress markers in both mesenteric arteries and plasma samples. The antioxidant activity, serum superoxide dismutase and catalase were significantly reduced, whereas malondialdehyde was increased in the high-salt offspring. O2 production, and protein expression of Nox2 and Nox4 in mesenteric arteries was significantly increased in the high-salt offspring whereas Nox1 showed no changes. The local renin–angiotensin system in mesenteric arteries was activated, associated with an increased NADPH oxidase. DNA methylation at the proximal promoter of angiotensin-converting enzyme gene in the lung was significantly increased in the high-salt offspring (P = 0.004).Conclusion:The results suggest that prenatal high-salt diet impairs nitric oxide-mediated vasodilatation because of the increased oxidative stress-affected renin–angiotensin system in the high-salt offspring, providing new information for understanding, and early prevention of cardiovascular diseases in fetal origins.

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