Low birth weight in response to salt restriction during pregnancy is not due to alterations in uterine-placental blood flow or the placental and peripheral renin-angiotensin system.

A number of studies conducted in humans and in animals have observed that events occurring early in life are associated with the development of diseases in adulthood. Salt overload and restriction during pregnancy and lactation are responsible for functional (hemodynamic and hormonal) and structural alterations in adult offspring. Our group observed that lower birth weight and insulin resistance in adulthood is associated with salt restriction during pregnancy. On the other hand, perinatal salt overload is associated with higher blood pressure and higher renal angiotensin II content in adult offspring. Therefore, we hypothesised that renin-angiotensin system (RAS) function is altered by changes in sodium intake during pregnancy. Such changes may influence fetoplacental blood flow and thereby fetal nutrient supply, with effects on growth in utero and, consequently, on birth weight. Female Wistar rats were fed low-salt (LS), normal-salt (NS), or high-salt (HS) diet, starting before conception and continuing until day 19 of pregnancy. Blood pressure, heart rate, fetuses and dams' body weight, placentae weight and litter size were measured on day 19 of pregnancy. Cardiac output, uterine and placental blood flow were also determined on day 19. Expressions of renin-angiotensin system components and of the TNF-alpha gene were evaluated in the placentae. Plasma renin activity (PRA) and plasma and tissue angiotensin-converting enzyme (ACE) activity, as well as plasma and placental levels of angiotensins I, II, and 1-7 were measured. Body weight and kidney mass were greater in HS than in NS and LS dams. Food intake did not differ among the maternal groups. Placental weight was lower in LS dams than in NS and HS dams. Fetal weight was lower in the LS group than in the NS and HS groups. The PRA was greater in LS dams than in NS and HS dams, although ACE activity (serum, cardiac, renal, and placental) was unaffected by the level of sodium intake. Placental levels of angiotensins I and II were lower in the HS group than in the NS and LS groups. Placental angiotensin receptor type 1 (AT(1)) gene expression and levels of thiobarbituric acid reactive substances (TBARS) were higher in HS dams, as were uterine blood flow and cardiac output. The degree of salt intake did not influence plasma sodium, potassium or creatinine. Although fractional sodium excretion was higher in HS dams than in NS and LS dams, fractional potassium excretion was unchanged. In conclusion, findings from this study indicate that the reduction in fetal weight in response to salt restriction during pregnancy does not involve alterations in uterine-placental perfusion or the RAS. Moreover, no change in fetal weight is observed in response to salt overload during pregnancy. However, salt overload did lead to an increase in placental weight and uterine blood flow associated with alterations in maternal plasma and placental RAS. Therefore, these findings indicate that changes in salt intake during pregnancy lead to alterations in uterine-placental perfusion and fetal growth.

Insulin resistance due to chronic salt restriction is corrected by alpha and beta blockade and by L-arginine.

Dietary salt restriction is associated with evidence of low insulin sensitivity. The current study was undertaken to investigate whether sympathetic nervous system and l-arginine-nitric oxide pathway activities are linked to insulin resistance in rats under chronic low salt intake. Male Wistar rats were fed a low (LSD) or normal (NSD) salt diet from weaning to adulthood. A euglycemic hyperinsulinemic clamp was performed in 4 sub-groups on each diet: (1) sympathetic nervous system blockade (propranolol and prazosin), (2) vehicle, (3) L-arginine, and (4) D-arginine. Blood pressure, heart rate and metabolic measurements were done before and 45 min after drug infusion and at the end of the clamp. At baseline conditions, body weight, hematocrit, blood glucose, plasma insulin, cholesterol, and triacylglycerols were higher in LSD than in NSD rats. Systolic blood pressure was lower and heart rate was higher in rats on LSD than on NSD. Glucose uptake was lower on LSD compared to NSD. Sympathetic nervous system blockade and L-arginine did, and vehicle and D-arginine did not improve glucose uptake in LSD rats. On NSD there was no effect of any of the infused drugs. A positive correlation between plasma nitrate and nitrite at the end of clamp and glucose uptake was observed in L-arginine--but not in D-arginine-infused LSD rats. These results provide evidence that the sympathetic nervous system and the L-arginine-nitric oxide pathway are involved in the glucose uptake impairment induced by chronic dietary salt restriction.

Sobrecarga e restrição de sal na dieta durante a gestação em ratas wistar: efeitos sobre o sistema renina-angiotensina, função renal, resistência à insulina e pressão arterial / Dietary salt overload or restriction during gestation in wistar rats: effects on the renin-angiotensin system, renal function, insulin resistance and blood pressure

Diversos estudos epidemiológicos têm relacionado doenças na vida adulta, como diabetes tipo-2 e hipertensão, e ambiente inadequado durante a vida fetal. Fatores distintos relacionados aos hábitos alimentares, como ingestão de sal na dieta, podem ter impacto importante no período perinatal. Recentemente, demonstramos que dieta hipossódica (HO) durante a gestação está associada com baixo peso ao nascimento e alterações na vida adulta. O objetivo do presente estudo foi avaliar o efeito da dieta HO e hipersódica (HR) durante gestação em ratas. Ratas Wistar foram alimentadas com dieta HO, dieta normossódica ou HR desde a 8ª semana e foram acasaladas com 12 semanas de idade. Estes animais foram estudados na terceira semana de gestação e um grupo adicional de ratas virgens foi estudado como controle para o efeito da gestação. O peso da placenta e o do feto e o fluxo sanguíneo uterino foram menores e a resistência vascular periférica foi maior no grupo HO. Maior peroxidação lipídica e expressão gênica do receptor AT1 na placenta foram observadas no grupo HR. Em conclusão, peso do feto, peso da placenta e fluxo sanguíneo uterino são influenciados pelo consumo de sal durante a gestação.

Many epidemiological studies have linked diseases in adulthood, such as type-2 diabetes and hypertension, to adverse intrauterine environment during fetal life. Distinct factors related to dietary habits, such as salt intake, may have a major impact on the perinatal period. Recently, we have demonstrated that low-salt diet (LSD) during pregnancy is associated with low birth weight and diseases during adulthood. The aim of this study was to evaluate the effect of LSD and high-salt diet (HSD) during pregnancy in rats. Female Wistar rats were fed with LSD, normal-salt diet or HSD since 8 weeks of age and matted with 12 weeks of age. These animals were studied at the third week of gestation and one additional group of virgin rats was evaluated as a control for the gestation effect. Placenta and fetus weight and uterine blood flow were lower and peripheral vascular resistance was higher in the LSD group. In the placenta from HSD rats, higher lipid peroxidation and AT1 receptor mRNA were observed. In conclusion, fetal weight, placenta weight and uterine blood flow are influenced by the degree of salt consumption during pregnancy.