EARLY ARTERY REMODELING IN RATS WITH FETAL ZINC RESTRICTION

C. ARRANZ ; R. SANCHEZ; L. VEIRAS; S. MASSARA,; M. CERNIELLO; A. TOMAT

MILAN

Congreso; 21st EUROPEAN MEETING ON HYPERTENSION AND CARDIOVASCULAR PREVENTION; 2011

We have shown that inadequate zinc intake during fetal life and lactation programs hypertension and kidney morphological and physiological alterations in adult rats. Moreover, in young rats we observed myocytes remodelling and reduced NO synthase (NOS) activity in males (m) and females (f) rats. Objective: To evaluate vascular alterations in growing and adult zinc deficient rats and to compare the effects in m and f rats. 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 6, 21 and 81, m and f offspring of each group of mothers (Cm, Lm, Cf and Lf) were sacrificed to perform morphological studies in thoracic aorta sections stained by heamatoxylin-eosin (intima thickness(ìm); media thickness(ìm)) and picrosirius red (perivascular collagen thickness(ìm), and signs of fibrosis in the media layer). NOS activity with L-(U14C)-arginine was also determined in thoracic aorta at 21 and 81 days. Results: Zinc deficient rats showed reduced vascular NOS activity (pmol Cit/g tissue.min) at 21 (C: 225 ± 4; L: 172 5*) and 81 days (C: 231 ± 5; L: 167 ± 6*). Perivascular collagen thickness was increased in Lm and Lf since day 21 (Cm:16±1;Lm:24±1*;Cf:12±1;Lf:23±2?) up to 81 days (Cm:46±1;Lm:71±6*;Cf:43±1;Lf:64±2?).No signs of fibrotic processes were observed in the media layer of the thoracic aorta in any of the experimental groups.*p<0.01vsCm; ?p<0.01vsCf, # p<0.01 vsLm. n=6 for each group. Conclusion: Zinc restriction during fetal life and postnatal growth induces a hypotrophic remodeling of large arteries that was observed since early postnatal life and persisted until adulthood. These alterations were accompanied by an increase of the perivascular collagen and were similar in male and female offspring.The decrease of vascular NOS activity and the inadequate growth in conduct arteries would impair vascular smooth muscle relaxation and would be reflected in a normal or abnormal posnatal vascular function in response to increases in flow and in shear stress.