Effects of a Hypersaline Sodium-rich Carbonated Natural Mineral Water on Structure and Expression of VEGF, VEGFR1, VEGFR2, Ang1, Ang2 and Tie2 of Fructose-treated Rat Corpus Cavernosum

Abstract

Metabolic Syndrome (MS) definition is based on a cluster of metabolic risk factors that identifies subjects at high risk for forthcoming type 2 diabetes mellitus and atherosclerotic cardiovascular diseases (CVD). Although the exact aetiology of the MS still remains unclear, it is known to involve complex interactions between genetic, metabolic and environmental factors, with diet and oxidative stress playing important roles. Regular increased fructose consumption has been associated to some metabolic adverse changes observed in the MS and, thus, fructose-fed is considered a suitable animal model of diet-induced MS. On the other hand, calcium, magnesium and potassium, generally deficient in MS-inducing diets, and abundant in natural mineral-rich waters, have been proposed protective against the MS. Although their exact effects are not yet fully clarified, natural mineral-rich waters present some antioxidant properties that exert protection against reactive oxygen species that are chief contributors to the increase of CVD risk, considering their reactivity to nitric oxide (NO). Such waters also improve some MS metabolic risk factors. Degradation of NO seriously compromises the vasodilatation mechanism leading to endothelial dysfunction, which always precedes atherosclerosis — the main contributor to CVD and erectile dysfunction. Penis erection is a vascular process that strongly depends on NO-induced smooth muscle relaxation. Moreover, NO mediates indirectly the vascular endothelial growth factor (VEGF)-induced angiogenesis, which is fundamental to maintain endothelium integrity in the cavernous tissue. VEGF binds specifically to VEGF tyrosine kinase membrane receptors (VEGFR1 and VEGFR2), and crosstalk in vivo with other angiogenic factors such as angiopoietins that compete for binding to the endothelial-specific Tie2 receptor. Previous work from our group demonstrated that long-term consumption of antioxidant-rich beverages modifies the expression of VEGF, Ang1, Ang2 and their receptors VEGFR1, VEGFR2 and Tie2 in the cavernous tissue of the rat, preventing atherosclerosis progression.