STUDY OF CARDIAC FUNCTION AND RENIN-ANGIOTENSIN SYSTEM IN A FETAL PROGRAMMING MODEL OF MODERATE ZINC DEFICIENCY IN ADULT RATS

MARIA NATALIA GOBETTO; MANUELA ALADRO; LORENA JURIOL; FACUNDO MENDES GARRIDO; LUIS GONANO; MALENA MORELL; MARIELA GIRONACCI; ROSANA ELESGARAY; MARTIN VILA PETROFF; CAROLINA CANIFFI; ANALIA TOMAT; CRISTINA ARRANZ

Rio de Janeiro

Congreso; IUPS 38th World Congress; 2017

The physiological society

Moderate zinc deficiency during intrauterineand postnatal growth induces low birth weight, hypertension and cardiovasculardysfunction in adult male rats. The cardiac renin angiotensin system (RAS)exerts an important modulating effect on cardiac function and development. Thisstudy?s aim was to evaluate cytosolic Ca2+ management and cell shortening inisolated cardiomyocytes; as well as the RAS in the left ventricle (LV) of maleand female adult rats exposed to a low zinc diet during fetal life, lactationand/or growth. Female Wistar rats received low (L:8ppm) or control (C:30ppm)zinc diet during pregnancy up to weaning. After weaning, male (m) or female (f)L offspring, received low (l) or control (c) zinc diet during 60 days (Llm,Llf, Lcm, Lcf). C offspring continued with control (c) zinc diet (Ccm, Ccf). Atday 81 of life we evaluated in LV: transient increase of cytosolic Ca2+ duringsystole (TICa: Fura-2 (340/380nm)) and shortening in electrically stimulatedisolated cardiomyocytes (CS:% of max length, Epifluorescence microscopy), ACEmRNA expression (ACE/GADPH, RTqPCR), expression of AT1 and AT2 receptors(optical density/actin WB) and concentrations of Angiotensin II and 1-7 (AII,A1-7 nM/g tissue, RIA). Values are mean±SEM, n=6/group. Two-way ANOVA,Bonferroni post-test. *p<0.05 vs. Ccm; §p<0.05 vs Lcm. Llm presented lessCS than Ccm (5.8±0.7* vs 10,6±1.5). Llm and Lcm had lower TICa (0,13±0,03*,0,19±0.01* vs 0,34±0,03), while AT1 levels in Llm and Lcm were higher than  in Ccm group (1,32±0,04*§, 1,81±0,09* vs1,00±0,07). AT2 was higher only in Llm (1,37±0,06* vs 1,00±0,01), as well asAII levels (14,27±0,45*§ vs 4,31±1,43 and 2,34±0,29). No differences were foundin A1-7 and ACE mRNA levels. Females did not present significant differences inany of the measured parameters. Zinc is an important micronutrient for cardiacdevelopment and function. Llm presents an altered inotropic state associatedwith decreased availability of cytosolic Ca2+ and impaired CS. They alsopresent increased AT1 and AT2 receptor expression, and AII concentration in theLV. The restitution of an adequate zinc supply after weaning partially reversesthese changes. Females seem more protected against zinc deficiency, as they didnot present changes. Alterations of the cardiac RAS could contribute to cardiacdysfunction in these adult animals.