Fetal zinc deficiency: Influence on renal nitric oxide and oxidative stress.

ARRANZ CRISTINA; SOFÍA AGUIRRE; LUCÍA SAVIGNANO; DANIELA CARDELLI ALCALDE; FACUNDO MENDES GARRIDO; MYRIAM MAC LAUGHLIN; ROSANA ELESGARAY; CAROLINA CANIFFI; COSTA MARÍA ÁNGELES; TOMAT ANALÍA

Congreso; 21st European Meeting on Hypertension and Cardiovascular Prevention, European Society of Hypertension; 2011

Moderate and marginal zinc deficiency during pregnancy is a nutritional insult to fetal and postnatal development. We have demonstrated that moderate zinc deficiency in rats during intrauterine and postnatal growth is also a model of fetal programming of hypertension and renal diseases in adult life. At weaning, fetal and lactation zinc deficiency induced a reduction in glomeruli number and a compensatory hypertrophy in the remaining nephrons. Objective: To evaluate renal nitric oxide system and oxidative stress at 21 days of life and to determine if there are sex differences in response to fetal and lactation zinc deficiency. Methods: Wistar rats were exposed from the beginning of pregnancy up to adulthood: low (L, 8 ppm) or control(C, 30 ppm) zinc diet. At day 21, male (m) and female (f) offspring of each group of mothers (Cm, Lm, Cf and Lf) were sacrificed to determine renal nitric oxide synthase (NOS) activity with L-(U14C)-arginine (pmol/min~g tissue) and protein abundance by western blot (% density/ƒÀ actin). Renal oxidative stress was evaluated measuring thiobarbituric acid-reactive substances (TBARS), glutathione concentration (GLUT), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase activity (GPx). Results: Renal NOS activity was decreased in Bm (237}5) and Bf (245}7) compared with Cm (302}5) and Cf (317}11) respectively.  Renal eNOS content was higher in Bm (43.2}1.9% ;p<0.01) than Cm (29.7}1.9%), but Bf (42.1}3.8) and Cf (35.7}1.2) showed no differences.*p<0.01vs Cm;ö p<0.01vs Cf. n=6 for each group. Conclusions: Zinc is essential for all stages of early development. Kidney morphological alterations observed in this model may be associated with nitric oxide system and oxidative stress alterations.The lower renal NOS activity observed in zinc deficient rats is not due to a decrease in, at least, eNOS protein expression. So we suggest that other mechanisms may be involved, like the alteration in NOS zinc cluster and the cofactors of the NOS or the increase in oxidative stress. Moreover, in male rats the increase in eNOS expression may be compensatory mechanism. The impairment of antioxidant enzymes due to this deficiency is more evident in female than in male rats Conclusions: Zinc is essential for all stages of early development. Kidney morphological alterations observed in this model may be associated with nitric oxide system and oxidative stress alterations.The lower renal NOS activity observed in zinc deficient rats is not due to a decrease in, at least, eNOS protein expression. So we suggest that other mechanisms may be involved, like the alteration in NOS zinc cluster and the cofactors of the NOS or the increase in oxidative stress. Moreover, in male rats the increase in eNOS expression may be compensatory mechanism. The impairment of antioxidant enzymes due to this deficiency is more evident in female than in male rats