High salt exacerbates programmed hypertension in maternal fructose-fed male offspring

•Maternal high-fructose (HF)-induced programmed hypertension in male offspring.•Postnatal high-salt (HS) intake aggravated HF-induced programmed hypertension.•HF and HS-induced programmed hypertension is ADMA-NO independent.•HF and HS regulated the components of renin-angiotensin system differentially.•Postnatal HS but not prenatal HF increased renal protein abundance of NHE3, NCC, and NKCC2.

Background and aimsConsumption of food and drinks containing high fructose (HF), which is associated with hypertension, is increasing steeply. Moreover, increased salt intake significantly increases hypertension risk. We examined whether maternal HF and postnatal high salt (HS) intake had synergistic effects on blood pressure (BP) elevation in adult offspring and determined the underlying mechanisms.Methods and resultsPregnant Sprague-Dawley rats received regular chow or chow supplemented with 60% fructose during the entire pregnancy and lactation periods. Half of the male offspring received 1% NaCl in drinking water from weaning to 3 months of age. Male offspring were assigned to 4 groups (control, HF, HS, and HF + HS) and were sacrificed at 12 weeks of age. Offspring in HF and HS groups developed hypertension, indicating that HF and HS synergistically increased BP. Postnatal HS intake increased Ace expression and decreased Agtr1b and Mas1 expression in the kidneys. Renal mRNA levels of Ace and Agtr1a were significantly higher in HF + HS group than in control group. Renal levels of Na-K-2Cl cotransporter, type 3 sodium hydrogen exchanger, and Na+/Cl− cotransporter were higher in HS and HF + HS groups than in control group.ConclusionPostnatal HS intake exacerbated prenatal HF-induced programmed hypertension. HF and HS induced programmed hypertension by differentially inducing renin-angiotensin system and sodium transporters in the kidneys. Better understanding of the effect of the relationship between HF and HS on hypertension development will help prevent hypertension in mothers and children exposed to HF and HS.