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  • In conclusion the results obtained in this study and


    In conclusion, the results obtained in this study and those recently reported by our group (Abdel-Samad et al., 2012) clearly indicate that a dialogue indeed exists between the systems of NPY and ET-1 at the level of human endocardial endothelial cells, since these cells, whether isolated from the right or the left ventricle, secrete ET-1 upon stimulation with NPY. The existence of interactions or crosstalk between two cardioactive mediators is not uncommon (Abdel-Samad et al., 2012). Evidence in the literature about complex interactions between the different vasoconstrictors and vasodilators has become plentiful, particularly reports about the interactions between ET-1, AngII and NO at the level of the heart and blood vessels. AngII is known to stimulate the production and release of ET-1, whereas NO has been reported to inhibit it. On the other hand, ET-1 was demonstrated to elicit the release of NO. However, there are no reports, to our knowledge, showing that a dialogue exists between the systems of NPY and ET-1, be it in the heart or blood vessels. To be accurate, Hoang et al. in the year 2002 investigated the role of ET-1 on the evoked release of NPY from sympathetic neurons using a perfused rat mesenteric arterial bed. He showed that ET-1 was able to attenuate NPY release, upon high frequency nerve stimulation. The ET-1-induced inhibition of NPY appeared to be mediated by the ETB receptor (Hoang et al., 2002). Our results confirm our previous findings (Abdel-Samad et al., 2012) that a crosstalk can and does exist between these 2 peptides in the cardiovascular system, and particularly in the endothelial MK2 Inhibitor IV that line the ventricular cavities of the human heart. The existence of such crosstalk in the endocardial endothelium, which is known for its very close proximity to the underlying myocardium, serves to endorse the important and rather indispensable role that these cells play in regulating cardiac growth, contractile performance and rhythmicity (Brutsaert, 2003). Recently, results obtained by our group have demonstrated that hEECs are able to secrete NPY into the extracellular medium and that this peptide can induce an increase in the [Ca]i of these cells (Jacques et al., 2003b). In light of these results and those obtained in this study, we can speculate that the released NPY can then act in a paracrine fashion on the subjacent cardiomyocytes, or in an autocrine fashion on hEECs themselves to maintain its own secretion and/or induce the release of other peptides such as ET-1 (Abdel-Samad et al., 2012, Jacques and Abdel-Samad, 2007). The luminal secretion by EECs of both these peptides into the ventricular cavity may affect their arterial circulating levels, whereas their abluminal secretion into the subendocardial space or the extracellular matrix located between hEECs and the underlying myocardium would certainly contribute to normal functioning of the heart (Abdel-Samad et al., 2007, 2012). Furthermore, overstimulation of NPY or ET-1 secretion by hEECs may lead or contribute to abnormal heart function such as arrhythmia, hypertrophy and heart failure (Jacques and Abdel-Samad, 2007, Abdel-Samad et al., 2007). In fact, the correlation between elevated plasma levels of NPY and ET-1 on one hand and cardiac and vascular pathophysiological states on the other hand has been documented in the literature. Increased NPY concentrations were reported in cases of hypertension and high plasma NPY immunoreactivity was detected in patients with acute myocardial ischemia (Ullman et al., 1994a) and congestive heart failure (Ullman et al., 1994b). The EEC secreted blood borne NPY and ET-1 could be the result of a cross talk between the sympathetic nerves controlled by the central nervous system and EECs (Marron et al., 1994). The secreted blood borne NPY and ET-1 would contribute to cardiovascular function in health and disease directly or indirectly via their crosstalk with circumventricular organs modulating the activity of the brain cardiovascular centers (Ufnal and Skrzypecki, 2014). Therefore, released hormones by EECs at the exit of the heart as well as the tuning of the level of these hormones at the entrance of the arterial circulation would contribute, along with the nervous system, to not only the excitation-secretion coupling of EECs and the excitation-contraction coupling of cardiomyocytes (Abdel-Samad et al., 2012, Brutsaert and Andries, 1992, Shah et al., 1996, Jacques et al., 2003a, Jacques et al., 2003b), but also the physiological and pathophysiological states of both heart and vascular systems.