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In fact, the more significant hemodynamic effects of this agents, conveyed by TGF restoration, led to afferent arteriole vasoconstriction as compared to efferent vasodilation observed with RAS-inhibition ( Pre-clinical studies in genetically modified animal model of T2DM (OLETF rats, Otsuka Long Evans Tokushima fatty rats) have shown high PRA (plasmatic renin activity) levels, without any change in aldosterone levels under dapagliflozin chronic treatment, in accordance with the aforementioned observations of an independent intrarenal RAS ( Moreover, in recent years the use of small interfering RNAs (siRNA), selectively targeting AGT, as a novel approach of interfering with the RAS has shown beneficial cardio- and nephroprotective properties

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These findings provided a better understanding of the physiology of GLP-1 and the pharmacology of its analogues and have revolutionized the management of obesity and several comorbidities