Vascular risk factors programmed by zinc deficiency during prenatal and postnatal life in male rats

MENDES-GARRIDO F; GOBETTO MN; CASTAÑÓN A; ELESGARAY R; TOMAT AL; ARRANZ,C

Congreso; XXIII CONGRESO ARGENTINO DE HIPERTENSIÓN ARTERIAL; 2016

Sociedad Argentina de Hipertensión Arterial

Background: Nutrient restrictionduring fetal growth may predispose to the development of hypertension in adultlife. In Argentina 52% of pregnant women present an inadequate zinc intake (1).Our group has demonstrated that moderate zinc deficiency during intrauterinelife and postnatal growth programs cardiac and renal alterations in adult life(2). Objective: We evaluated if zinc deficiencyinduces early vascular alterations in newborn rats that persist into adulthood. Methods: Wistarrats received during pregnancy up to weaning low (L:8ppm) or control (C:30ppm)zinc diet. At day 6 of life some L or C male offspring were sacrificed. Afterweaning, males fed low (l) or control (c) zinc diet (Cc, Ll, Lc) until day81. We evaluated morphology of thoracic aorta and intrarenal resistancearteries (M/L, media/lumen areas ratio, Sirius red staining), activities ofaortic Nitric Oxide Synthase (NOS, pmol 14C-L-Citrulline/gtissue.min) and NADPH oxidase (AU/g tissue, chemiluminescence method) andaortic lipid peroxidation (nmol MDA/mg prot, TBARS assay). At day 81 wemeasured systolic blood pressure (SBP,mmHg, tail-cuff technique). In aorticrings suspended in Krebs solution we evaluated maximal contraction tophenylephrine (PE,10-9-10-5M), angiotensin-II (Ang-II,10-10-10-6M)and caffeine (25mM) as % of KCl 90mM contraction. In rings preconstricted withPE 10-5M we measured the maximal relaxation with acetylcholine(ACh,10-10-10-3M) and sodium nitroprusside (SNP,NOdonor,10-11-10-5M).  Results:   6 days L C Body weight (g) 12.6±0.6 10.2±0.3* Renal arteries M/L 4.1±0.4 6.8±0.5* Aortic M/L 67±8 60±8 NOS 136±3 86±3* TBARS 0.27±0.03 0.59±0.07*   Student?s t-test,*p<0.05 vs C(n=6/group)  81 days Cc Ll Lc SBP 126±1 143±1* 146±2* Renal arteries M/L 3.9±0.3 10±1*? 4.8±0.8 Aortic M/L 23.3±0.6 23.3±0.4 23.7±0.6 NOS 225±5 172±4* 160±8* TBARS 0.23±0.03 0.27±0.03 0.26±0.01 NADPH oxidase 667±77 740±35 759±90 ACh 90±1 76±5* 77±3* SNP 108±2 115±1 114±2 PE 76±5 53±5*? 73±7 Ang-II 32±3 23±2* 25±2* Caffeine 39±3 27±2* 28±2*  ANOVA,Bonferroni post-test,*p<0.05 vs Cc,?p<0.05 vs Lc (n=6/group). AChresponse was abolished in endothelium-denuded rings or by incubation withL-NAME 1mM (NOS inhibitor). Discussion: Zincdeficiency induces a remodelling in renal small arteries and a reduced aorticNOS activity in newborn rats that persist in adult life. Adult rats showed anaortic hyporesponsiveness to ACh due to a lower endothelial NO production butnot to a pro-oxidant state. The reduced contractile response to Ang-II and PEwould be associated with intracellular calcium mobilization alterations(caffeine experiments). Adequate zinc during post-weaning growth could notrevert all vascular alterations. Our study is consistent with the hypothesis offetal programming of hypertension and highlights the relationship between goodnutrition and cardiovascular health.  Quotes: 1:Argentinian Health Ministry, 2008, National Survey on Nutrition and Health. 2:Tomat et al, 2011, Nutrition 27(4):392-8