Maternal zinc restriction causes gender related alterations in renal ras in early stage of life and in the adulthood

ARRANZ C; GOBETTO MN; JURIOL L; DASSO M; MENDES-GARRIDO F; CARDELLI ALCALDE D; RADIONOVAS V; GIRONACCI M; TOMAT AL

Milán

Congreso; 25th European Meeting on Hypertension and Cardiovascular Protection; 2015

European Society of Hypertension

A moderate zinc deficient diet during pregnancy and/or growth induce, low birth weight, hypertension and renal dysfunction in rat adulthood. This is most evident in males than in females. The aim of this study was to evaluate the renal renin­angiotensin system (RAS) in early stages of development and in adulthood of male and female rats exposed to a moderately zinc ­deficient diet during fetal and/or postnatal growth. Female Wistar rats received during pregnancy up to weaning low (L:8ppm) or control (C:30ppm) zinc diet. After weaning, the offspring L, male (m) or female (f) received fed low (l) or control (c) zinc diet during 60 days (Llm, Llf, Lcm, Lcf). The offspring C continued with fed control (c) zinc diet (Ccm, Ccf). At day 6 of life (a group of rats: Cm, Cf, Lm and Lf), we evaluated in renal tissue: AngII receptor (AT1R) and angiotensin­converting enzyme (ACE) by western blot (WB, OD) and Angiotensin II (AngII) by radioimmunoassay. At day 81, we evaluated in renal cortex: AT1R by WB (OD) and immunohistochemistry (IHC), ACE mRNA expression by RTqPCR and AngII by radioimmunoassay Results The IHC of receptor AT1 showed staining specified mainly in proximal and distal tubules. Values are means±SEM, n=6/group. Two way ANOVA, Bonferroni post­test. # p<0,05 vs. Cm; *p<0,05 vs. Ccm; In early stages of development, a dietary zinc deficiency disrupts the normal functioning of the RAS increasing the production of AngII and ACE. In adult rats receiving nutritional insult during whole life, this system continues altered as shown by the increased levels of AngII and AT1R. This was only observed in male rats. When this restriction is lifted after maturity, this activation appears to be partially reversed. However these rats maintain elevated Systolic Blood Pressure and AT1R levels. The upregulation of RAS may be a compensatory response to the suboptimal prenatal zinc intake and could explain the alterations induced during organ development that persist in adult life and may be associated with inflammatory and fibrotic processes of the kidney.