Exposure to zinc deficiency in fetal and postnatal life determines nitric oxide system activity and arterial blood pressure levels in adult rats

Abstract

We had previously shown that prenatal exposure to Zn-deficient diets induces an increase in blood pressure and impairs renal function in adult rats. The aim of the present study was to investigate if moderate Zn restriction during early growth periods, fetal life and lactation would induce impairment in the vascular and renal NO system and alterations in plasma lipid profile. We also investigated if these effects persisted into adult life, even when a Zn-replete diet was provided after weaning. Pregnant rats were fed control (30 parts per million (ppm)) or low (8 ppm) Zn diets throughout gestation up to weaning. Afterwards, male offspring from low-Zn mothers were assigned to low-or control-Zn diets during 60 d. Male offspring from control mothers were fed a control diet. Animals exposed to Zn restriction showed low birth weight, increased systolic blood pressure and serum TAG levels, and decreased glomerular filtration rate in adulthood. Zn restriction induced a decrease in vascular and renal NO synthase activity and a reduced expression of the endothelial NO synthase isoform in aorta. A control-Zn diet during post-weaning growth returned TAG levels to normal but was unsuccessful in normalising systolic blood pressure, glomerular filtration rate or NO system activity in Zn-deficient offspring. Zn restriction during fetal life, lactation and/or post-weaning growth induced alterations in the vascular and renal NO system and in lipid metabolism that could contribute to the programming of hypertension and renal dysfunction in adulthood.Arterial blood pressure: Nitric oxide system: Moderate zinc restriction: Fetal life Human epidemiological and experimental studies have provided considerable evidence to suggest that nutritional imbalance and metabolic disturbances during critical developmental time windows have persistent effects on the health of the offspring and may be responsible for in utero programming of common disorders such as obesity, diabetes and hypertension in adult life (1 -3) . Moderate and marginal Zn deficiency observed in pregnant women could be a nutritional insult to fetal and postnatal development (4,5) . Moreover, this micronutrient could program adult pathologies by an epigenetic mechanism since it controls methylation reactions and epigenetic modifications of DNA and histones (6,7) .Zn is found in a wide variety of foods such as whole-grain cereals, legumes, meat, chicken and fish. However, moderate Zn deficiency is mostly due to nutritional imbalances in those stages of life when Zn requirements are increased, such as postnatal growth and pregnancy (5,8) .We had previously reported that moderate Zn restriction during fetal life, lactation and/or post-weaning growth of rats induces an increase in arterial blood pressure (BP) and impairs renal function in adult life. These alterations were associated with an increase in renal oxidative stress, activation of renal apoptosis and fibrosis, and a reduction in the renal filtration surface area (9) . Moreover, we also reported that animals exposed to...

Morphological and functional effects on cardiac tissue induced by moderate zinc deficiency during prenatal and postnatal life in male and female rats

“…However, this alteration could not be prevented by an adequate zinc diet after weaning. This degree of blood pressure elevation dramatically increases the risk of cardiovascular events (40,41,42,44,48). Moreover, in the present study, we demonstrated, for the first time, that fetal and postnatal zinc restriction does not modify blood pressure levels in females.…”

“…Dietary zinc restriction during fetal life and lactation induces an increase in arterial blood pressure and impairs renal function in adult male rats (40,42,43).…”

High serum zinc and serum testosterone levels were associated with excessive erythrocytosis in men at high altitudes

“…Our study also showed that increased serum nitric oxide levels were also associated with low scores for signs and symptoms of CMS. Recently, it has been demonstrated that nitric oxide and Zn are endogenous signaling molecules acting in response to environmental stress [43,44].…”

Zinc and reproduction: effects of zinc deficiency on prenatal and early postnatal development

“…As observed in other cell types, zinc deficiency decreased activities and amounts of oxidant defense system components, increased oxidative damage to lipids, and increased apoptosis (Tomat et al, 2008). Moderate zinc deficiency during pregnancy and lactation also led to decreased nitric oxide synthase (NOS) activity in the vasculature of aortic artery and resistance arterioles, and in kidney nephrons that persisted into adulthood despite zinc repletion at weaning (Tomat et al, 2010). The expression of endothelial NOS (eNOS) in the thoracic aorta was lower in the low zinc groups compared to controls (Tomat et al, 2010).…”

“…Moderate zinc deficiency during pregnancy and lactation also led to decreased nitric oxide synthase (NOS) activity in the vasculature of aortic artery and resistance arterioles, and in kidney nephrons that persisted into adulthood despite zinc repletion at weaning (Tomat et al, 2010). The expression of endothelial NOS (eNOS) in the thoracic aorta was lower in the low zinc groups compared to controls (Tomat et al, 2010). Thus, maternal and lactational zinc deficiency leads to lower nitric oxide production and renal dysfunction in the offspring that persist into adulthood leading to increased risk for cardiovascular complications such as hypertension.…”