Maternal hypertension induced by NO blockade does not program adult metabolic diseases in growth-restricted rat fetuses.

ABSTRACT

OBJECTIVE: Preeclampsia is a frequent and potentially lethal placental insufficiency pathology causing maternal hypertension and proteinuria, as well as a high rate of intrauterine growth retardation (IUGR) in offspring. Reduced nitric oxide (NO) production may play a role in the mechanisms of this disease. As exposure to adverse early life environment and IUGR has been proposed to increase cardiometabolic diseases risk, we investigated in rats the effects of maternal NO blockade on growth and metabolic phenotype of offspring. MATERIAL AND METHODS: Osmotic pumps were implanted in pregnant rats at E17 and diffused saline or L-NAME (50mg/day), a nitric oxide synthesis inhibitor. At birth, IUGR male newborns without limb defects were selected. Body growth, feeding behavior and glucose tolerance were evaluated in offspring. Organs weights, plasma level of several metabolic hormones and genes expressions were determined in fasted 9month-old rats. RESULTS: L-NAME mothers had elevated blood pressure at E20. Male offspring from L-NAME mothers had a markedly reduced birth weight and developed postnatal catch-up growth during lactation. Some L-NAME newborns presented some limb defects but were not selected in this study (1/3 of all pups). Improved glucose tolerance and hyperphagia after fasting were found in 3-month-old L-NAME rat but not thereafter. In 9-month-old L-NAME rats, a moderate increase of food intake during the light phase and, after fasting, an augmentation of plasma insulin and a reduction of brown adipose tissue (BAT) deposit were found associated with an increased expression of UCP-1 mRNA in this tissue. CONCLUSIONS: Despite IUGR and postnatal catch up growth, male rats exposed to L-NAME did not develop metabolic diseases when limb defects were not induced by L-NAME. We postulate that maternal hypertension during late gestation is not a major 'programming' metabolic factor for offspring.