Developmental programming of vascular dysfunction by prenatal and postnatal zinc deficiency in male and female rats

Abstract

Micronutrient malnutrition during intrauterine and postnatal growth may program cardiovascular diseases in adulthood. We examined whether moderate zinc restriction in male and female rats throughout fetal life, lactation and/or postweaning growth induces alterations that can predispose to the onset of vascular dysfunction in adulthood. Female Wistar rats were fed low- or control zinc diets from pregnancy to offspring weaning. After weaning, offspring were fed either a low- or a control zinc diet until 81 days. We evaluated systolic blood pressure (SBP), thoracic aorta morphology, nitric oxide (NO) system and vascular reactivity in 6- and/or 81-day-old offspring. At day 6, zinc-deficient male and female offspring showed a decrease in aortic NO synthase (NOS) activity accompanied by an increase in oxidative stress. Zinc-deficient 81-day-old male rats exhibited an increase in collagen deposition in tunica media, as well as lower activity of endothelial NOS (eNOS) that could not be reversed with an adequate zinc diet during postweaning life. Zinc deficiency programmed a reduction in eNOS protein expression and higher SBP only in males. Adult zinc-deficient rats of both sexes showed reduced vasodilator response dependent on eNOS activity and impaired aortic vasoconstrictor response to angiotensin-II associated with alterations in intracellular calcium mobilization. Female rats were less sensitive to the effects of zinc deficiency and exhibited higher eNOS activity and/or expression than males, without alterations in SBP or aortic histology. This work strengthens the importance of a balanced intake of micronutrients during perinatal growth to ensure adequate vascular function in adult life.

Zinc deficiency induces hypertension by promoting renal Na+ reabsorption

“…Experimental studies also suggest that Zn 2ϩ may contribute to BP regulation (2,4,20,24). Epigenetic studies demonstrate that in utero ZnD predisposes rat offspring to hypertension (14,24). Specifically, ZnD in prenatal and postnatal rats induces BP derangements that are accompanied by cardiovascular and renal morphological and functional changes.…”

Fetal Undernutrition Induces Resistance Artery Remodeling and Stiffness in Male and Female Rats Independent of Hypertension

“…Sex differences in fetal programming of hypertension have been attributed to sex hormones, which exert actions on several blood pressure regulatory systems [ 29 ]. Among others, it has been reported that females exhibit better endothelial function [ 30 , 31 ], reduced responses to the renin-angiotensin system—which is downregulated by estrogens and amplified by testosterone—or better oxidative balance [ 17 , 18 ]. It is also possible that a lower MRA myogenic tone may contribute to maintain normal blood pressure level in females, despite the observed structural alteration.…”

Supportive treatment of vascular dysfunction in pediatric subjects with obesity: the OBELIX study

“…Another antioxidant, resveratrol , has shown beneficial effects on endothelial function since it has the ability to increase NO synthesis that, in vivo, plays an antioxidant function in the endothelium [ 18 – 20 ]. Animal models showed a relationship between prenatal and neonatal zinc deficiency and vascular dysfunction [ 21 , 22 ] keeping in mind that zinc has antioxidant-like properties in activated endothelium cells [ 23 ]. Magnesium, an essential mineral for human health, plays a role in endothelium function and participates in vascular calcification [ 24 ].…”