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

Abstract

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‐α (IL‐6;TNF‐α), basal NO synthase (NOS) and endothelial, neuronal and inducible (eNOS;nNOS;iNOS) isoforms activities; eNOS and Ser1177 eNOS phosphorylation protein expression (eNOS/β‐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‐α (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±0.02 0.74±0.03* 1.02±0.16 TBARS (nmol/mg protein) 0.21±0.02 0.78±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‐α, could contribute to the cardiac disorders previously observed. Supported by:UBA‐CONICET