Zinc deficiency during intrauterine and postnatal growth induces aortic morphological and functional alterations in rats

ARRANZ C; MENDES-GARRIDO F; GOBETTO MN; JURIOL L; DASSO M; WENK G; ELESGARAY, R; CANIFFI C; TOMAT AL

Atenas

Congreso; 24th European Meeting on Hypertension; 2014

European Society of Hypertension

Objective: Moderate zinc deficiency during intrauterine and postnatal growth induces an increase in blood pressure levels in adult males related to cardiovascular and renal disorders. Objective: To evaluate aortic morphology and function in adult male rats exposed to fetal and postnatal zinc deficiency. Design and method: Female 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 measured systolic blood pressure (SBP,mmHg, tail-cuff technique) and we evaluated the thoracic aorta morphology (Sirius red staining): artery area (Aa, mm2), media area/lumen area (Ma/La, %), collagen in tunica media (Fibrosis, arbitrary score, scale 0 to 4). In aorta we measured basal nitric oxide synthase (NOS) activity, and endothelial (eNOS), neuronal (nNOS) and inducible (iNOS) isoforms activities (pmol 14C-L-citrulline/g.tissue.min). In aortic rings, suspended in Krebs solution and preconstricted with phenylephrine 10-5M, we evaluated the maximal relaxation (ACh Emax, %) with acetylcholine (10-10 to 10-3 M); we also measured the maximal contraction with angiotensin-II (Ang-II Emax, % maximal contraction with KCl 90mM, 10-10 to 10-6 M). Values are means±SEM, n=6/group. One way ANOVA, Bonferroni post-test. Results: *p<0.01vs Cc; ?p<0.01vs Lc. Basal NOS activity was not affected by nNOS and iNOS inhibitors, but was decreased by blocking Ca2+-calmodulin (Cc:55±2#, Ll:64±1#, Lc:61±9#,#p<0.001 vs. basal) in all groups.  Conclusions: Zinc is an important micronutrient for arterial development and function. Moderate zinc deficiency during whole life is associated to a reduced aortic size with preserved Ma/La relation and higher signs of fibrosis in tunica media. Zinc deficiency during fetal and/or postnatal life programs a lower endothelial nitric oxide production that could explain the vascular hyporesponsiveness to ACh and an unexpected reduced contractile response to Ang-II probably due to alterations in Ang-II receptors in this model.