“Adenosine an old player with new possibilities in kidney diseases”: Preclinical evidences and clinical perspectives

Pharmacological Tuning of Adenosine Signal Nuances Underlying Heart Failure With Preserved Ejection Fraction

“…Adenosine has been reported to reduce urinary protein excretion ( Patinha et al, 2014 ), an earlier marker of underlying kidney injury causing renal dysfunction ( Katz et al, 2014 ), by acting at the kidney level (reviewed in ( Pandey et al, 2021 )). Specifically, adenosine controls renin release, glomerular filtration rate, tubuloglomerular feedback mechanism and vascular tone through all four P1 receptor subtypes.…”

“…The A 1 AR plays an important role in renal physiology, as it controls afferent arteriole vasoconstriction, reabsorption of sodium in the proximal tubule and the tubuloglomerular feedback. Through inhibition of renin release from justaglomerular cells along with renal arteriole vasodilation, adenosine (via A 1 AR) reduces renal blood flow lowering the glomerular filtration pressure ( Pandey et al, 2021 ), which is protective against kidney damage caused by metabolic diseases, such as diabetes and hypertension, often complicating HFpEF ( Lofman et al, 2017 ; Pandey et al, 2021 ). The salutary effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors, like empagliflozin, on diabetes-related hyperglycaemia, obesity and hypertension may be at least in part mediated by the reduction of glomerular hyperfiltration via activation of A 1 AR receptors and TGF-mediated afferent arteriolar vasoconstriction, independently of their ability to lower the plasma glucose levels ( Kidokoro et al, 2019 ).…”

“…These outcomes suggest the A 2A AR as a potential therapeutic target for the cardiorenal syndrome ( Chen et al, 2019 ). In addition to the anti-fibrotic role of the A 2A AR, its ability to dilate the efferent arteriole may be renoprotective by reducing the glomerular pressure ( Pandey et al, 2021 ). Long-term administration of the selective A 2A AR agonist, CGS21680, reduces diabetes-induced glomerular hyperfiltration in streptozotocin-treated diabetic mice through a mechanism depending on NO production ( Table 2 ) ( Persson et al, 2015b ).…”

“…In addition, A 1 AR activation has been associated to anti-ischemic properties by decreasing catecholamine release and ß -adrenergic overactivation ( Albrecht-Kupper et al, 2012 ; Greene et al, 2016 ). Activation of A 1 AR also improves the metabolic profile ( de Oliveira et al, 2020 ) and attenuates renal metabolic demand and glomerular filtration pressure ( Pandey et al, 2021 ). It is, therefore, not surprising that the most expressed adenosine receptor in the heart, the A 1 AR, has been the most widely studied receptor in cardiovascular, renal and metabolic diseases, both at preclinical and clinical levels ( Greene et al, 2016 ; Borah et al, 2019 ; Jacobson et al, 2019 ; Shah et al, 2019 ) (for details, see Pros and Cons of Adenosine A 1 Receptor Manipulation in HFpEF ).…”

Metabolomics Provides Insights into Renoprotective Effects of Semaglutide in Obese Mice

“…6,30-33 11, 12-Epoxyeicosatrienoic acid, Guanosine, Adenosine, and Adenosine 3'-monophosphate are associated with oxidative stress. [34][35][36][37][38][39] For verification of downstream physiological effects, we further assayed inflammatory and oxidative stress parameters.…”