Impact of Moderate Zinc Deficiency During Fetal Life and Postnatal Growth on Cardiac Nitric Oxyde System, Inflammatory and Oxidative Markers in Adult Male Rats

JURIOL L; GOBETTO MN; MENDES-GARRIDO F; PINEDA G; DASSO M; TOBLLI JE; CARRANZA MA; ELESGARAY R; TOMAT AL; ARRANZ C

Boston

Congreso; Experimental Biology; 2015

Moderate zinc deficiency during fetal and postnatal growth programs cardiovascular dysfunction and hypertension. Male zinc deficient rats showed reduced left ventricular (LV) wall thickness and ejection fraction. Aim: to evaluate nitric oxide (NO) system, pro-inflammatory cytokines and oxidative state in LV of adult male rats exposed to this deficiency. 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 evaluated in LV: Interleukin-6 and Tumor Necrosis Factor-á (IL-6;TNF-á), basal NO synthase (NOS) and endothelial, neuronal and inducible (eNOS;nNOS;iNOS) isoforms activities; eNOS and Ser1177 eNOS phosphorylation protein expression (eNOS/â-actin; pSer1177eNOS/eNOS), mRNA expression (eNOS/GAPDH) and lipid peroxidation end products (TBARS). Means±SEM, n=6/group. One way ANOVA, Bonferroni post-test. Cc Ll Lc TNF-á (immunohistochemistry;% of positive staining/area) 1.4±0.4 20.4±2.0* 1.7±0.3 IL-6 (immunohistochemistry; % of positive staining/area) 1.8±0.3 21.1±1.7* 2.8±0.8 Basal NOS Activity (pmol14C L-citrulline/g tissue.min) 204±6 164±10* 157±11* Basal NOS+iNOS inhibitor (Aminoguanidine; pmol14C L-citrulline/g tissue.min) 216±7 166±8* 163±9* Basal NOS+nNOS inhibitor (7-nitroindazole; pmol 14C L-citrulline/g tissue.min) 209±10 166±8* 164±9* Basal NOS+Ca2+-calmodulin inhibitor (Calmidazolium; pmol 14C L-citrulline/g tissue.min) 47±2# 52±2# 49±2# pSer1177eNOS/eNOS (Western Blot; optical density relative to Cc) 1.00±0.020.74±0.03*1.02±0.16 TBARS (nmol/mg protein) 0.21±0.020.78±0.08*0.47±0.02*? No differences were found in eNOS protein and mRNA expression. *p<0.01vsCc;?p<0.01vsLl;#p<0,01vs basal NOS. Zinc deficiency during fetal and postnatal life programs a lower production and bioavailability of cardiac NO due to decreased activity and pSer1177 of eNOS and increased TBARS. These alterations, jointly with higher levels of IL-6 and TNF-á, could contribute to the cardiac disorders previously observed. Supported by:UBA-CONICET