Moderate zinc deficiency during fetal life and postnatal growth: effect on cardiac NO system Pro-inflammatory cytokines and oxidative stress in male adult rats.

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

Buenos Aires

Congreso; International Congress of Translational Medicine. ¡§Cellular and Molecular Pathways as Therapeutic Target; 2014

International Master or Biomedical Sciences. Universidad de Buenos Aires, Argentina (Facultad de Medicina y Facultad de Farmacia y Bioqu¨ªmica), Res y la Universidad Albert Ludwigs, Friburgo, Alemania (Facultad de Medicina).

Moderate zinc deficiency during fetal life and postnatal growth: effect on cardiac NO system Pro-inflammatory cytokines and oxidative stress in male adult rats. Juriol LV1, Gobetto MN1, Mendes Garrido F1, Pineda G1, Dasso M1, Toblli J2, Carranza MA3, Elesgaray R1, Tomat A1, Arranz C1.1 Physiology Department. FFyB. UBA. IQUIMEFA-CONICET. 2 Hospital Alem¨¢n. 3 Pharmacology Department. FFyB. UBA. Moderate zinc deficiency during intrauterine and postnatal growth is a fetal programming model of hypertension, renal and cardiovascular dysfunction. 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 (eNOS), neuronal (nNOS) and inducible (iNOS) isoforms activities; eNOS and Ser1177 eNOS phosphorylation protein expression (eNOS/¦Â-actin, pSer1177eNOS/eNOS), mRNA expression (eNOS/GAPDH relative to Cc) and lipid peroxidation end products levels (TBARS). Values are means ¡À SEM, n=6/group. One way ANOVA, Bonferroni post-test.   Cc Ll Lc TNF-¦Á (immunohistochemistry;% of positive staining/area) 1.4¡À0.4 20.4¡À2.0* 1.7¡À0.3 IL-6 (immunohistochemistry;% of positive staining/area) 1.8¡À0.3 21.1¡À1.7* 2.8¡À0.8 Basal NOS Activity (pmol 14C L-Citrulline/g. tissue.min) 204¡À6 164¡À10* 157¡À11* pSer1177eNOS/eNOS (Western Blot; relative to Cc) 1.00¡À0.02 0.74¡À0.03* 1.02¡À0.16 TBARS (nmol/mg protein) 0.21¡À0.02 0.78¡À0.08* 0.47¡À0.02*? *p<0.01vs Cc; ?p<0.01vs Ll. NO production is mainly produced by eNOS, because basal NOS activity was not affected by nNOS and iNOS inhibitors, but was decreased by blocking Ca2+-calmodulin in all groups. 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 oxidative stress. Oxidative stress and NO impairment, jointly with higher levels of pro-inflammatory cytokines, could contribute to the cardiac disorders observed in adult males. Adequate zinc diet after weaning was unable to totally avoid the cardiac alterations induced during fetal life. Supported by: UBA-CONICET.