ZINC DEFICIENCY DURING INTRAUTERINE AND POSTNATAL GROWTH INDUCES AORTIC MORPHOLOGICAL AND FUNCTIONAL ALTERATIONS IN RATS

ARRANZ C; JURIOL L; GOBETTO MN; MENDES-GARRIDO F; PINEDA G; CARDELLI ALCALDE D; BRUNELLO F; RADIONOVAS V; ELESGARAY R; TOMAT AL

Atenas

Congreso; 24th European Meeting on Hypertension,; 2014

European Society of Hypertension

Objective: Moderate zinc deficiency during intrauterine and postnatal growth induces cardiovascular disorders in adult males, characterized by an increase in blood pressure levels and a decrease in wall thickness and left ventricular (LV) contractility. In turn, coronary arteries exhibited a hypertrophic remodeling associated with increased blood pressure.Objective: To evaluate nitric oxide (NO) system and oxidative stress levels in adult male rats exposed to fetal and postnatal zinc deficiency. Design and method: Design and method: Female Wistar rats received during pregnancy up to weaning low (L:8 ppm) or control (C:30 ppm) zinc diet. After weaning, male offspring fed low (l) or control (c) zinc diet during 60 days (Cc, Ll, Lc). At day 81, we measured systolic blood pressure (SBP,mmHg,tail-cuff technique) and we evaluated in LV: basal NOS and endothelial(eNOS), neuronal(nNOS) e inducible(iNOS) isoforms activities (pmol 14C L-citrulline/g.tissue.min); eNOS protein expression (western blot; optical density eNOS/â-actin relative to Cc) and mRNA expression (RT-qPCR; eNOS/GAPDH relative to Cc), lipid peroxidation end products (TBARS, nmol/mg protein) levels, catalase(pmol/mg protein), glutathione peroxidase(GPx, µmol/min.mg.protein), superoxide dismutase(SOD, USOD/mg protein) activities and glutathione concentration(GLUT, mg/mg protein). Values are means±SEM, n=6/group. One way ANOVA, Bonferroni post-test *p<0.01vs Cc; ?p<0.01vs Ll. Basal NOS activity was not affected by nNOS and iNOS inhibitors, but was decreased by blocking Ca2+-calmodulin(Cc:47±2#,Ll:52±2#,Lc:49±2#,#p<0.001 vs. basal) in all groups. Catalase activity is similar in all groups. Conclusions: Moderate zinc deficiency during fetal and postnatal life programs a lower production and bioavailability of cardiac NO, mostly, due to decreased activity of eNOS and increased levels of oxidative stress. The greater antioxidant enzymes activities would be a compensatory response to the increase in free radicals. Oxidative stress and NO impairment, jointly with other humoral, inflammatory and apoptotic mechanisms, could contribute to the cardiac disorders observed in adult males. Adequate zinc diet after weaning was unable to total avoid the cardiac alterations induced during fetal life.