For instance, it is well established that heart development is sensitive SB203580 to nutrition and hormonal changes during early life [28] and [51]. Results from the literature showed that obesity in early life leads to cardiac hypertrophy mainly due to increased cell size and protein synthesis. Consequently, the development of myocardial energy metabolism

and function impairment is associated with heart failure in adulthood. For instance, recent data from our group showed association between insulin signaling cascade impairment and cardiac hypertrophy in obese rats overnourished in early life [26] and [28]. Ghrelin is a 28-amino acid peptide released from the stomach bound to the endogenous ligand for the growth hormone secretagogue receptor (GHS-R) [22]. This hormone has been associated with several metabolic processes in different tissues. The most widely Galunisertib research buy known functions of ghrelin are the ability to increase GH secretion and stimulatory

effect on food intake and adiposity [10], despite the fact that ghrelin has been found reduced in obese individuals when compared to lean subjects [8]. This hormone has also been associated with modulation of metabolism in different tissues, including the heart. Ghrelin which was initially described in the hypothalamus, has been found in rat ventricles, atria, aorta, coronary and carotid arteries [13]. Different authors suggest that ghrelin may have an autocrine/paracrine function in cardiovascular tissues mainly associated with myocardial contractility, vasodilatation, and anti-inflammatory

effects. In addition, the cardiovascular action of the peptide in obese patients includes decreasing of blood pressure through central mechanisms and increasing of cardiac output without affecting heart rate. The direct vascular actions of ghrelin are diverse and seem to differ between species and vasculature of different organs. In clinical investigations ghrelin showed vasodilator characteristic: it increased forearm blood flow when given intraarterially [32] and reversed the constrictor effect Metformin in vivo of endothelin-1 (ET-1) in vitro on endothelium human mammary artery rings [20] and [52] and also induced vasodilation in phenylephrine-constricted perfused rat mesenteric vascular bed [27]. Indeed, vasoconstrictor effect of the ghrelin was studied, researchers found tone-dependent vasoconstrictor effect of ghrelin on human mesenterial and guinea-pig renal and femoral arterioles only when vessels were previously stimulated with ET-1 [14], [18], [33], [34] and [35]. It has been suggested that by restoring plasma ghrelin levels the organism may obtain cardiovascular protective effects as dilate peripheral blood vessels, constrict coronary artery, improve endothelial function, as well as inhibit myocardial cell apoptosis [56].