Fetal and postnatal zinc restriction: Impact on the cardiac inotropic state, the cardiac renin-angiotensin system, and sex differences.

The aim of this study was to determine the expression of peptides and enzymes of the cardiac renin-angiotensin system (RAS) and to evaluate changes in cytosolic Ca2+ and cellular shortening in isolated myocytes of the left ventricle (LV) in 81-d-old male and female offspring exposed to zinc deficiency during fetal life, lactation, and/or postnatal growth. Female Wistar rats were fed low- or control zinc diets during pregnancy and lactation. Twenty-one-d-old male and female offspring were fed a low- or a control zinc diet until 81 d of life. Angiotensin II and angiotensin 1 to 7 concentration, as well as angiotensin II type 1 receptor, angiotensin II type 2 receptor, angiotensin-converting enzymes proteins and/or mRNA expression were determined in the LV of 81-d-old offspring. Ca2+ transient and cell shortening were measured in isolated myocytes of the LV. In male offspring exposed to zinc restriction during intrauterine and postnatal life, the local cardiac angiotensin II/angiotensin-converting enzyme/angiotensin II type 1 receptor axis was up-regulated. Isolated cardiomyocytes showed a lower amplitude of Ca2+ transients associated with reduced shortening. An adequate diet during postnatal life cannot completely turn back the damaging effects of this micronutrient deficiency during prenatal and lactation periods. Female offspring showed no significant alterations in the cardiac RAS and the inotropic state of isolated cardiomyocytes. The present study demonstrates that zinc deficiency during fetal life, lactation, and/or postnatal growth could modulate, in a sex-specific manner, the cardiac RAS and the inotropic state of isolated cardiomyocytes.