This leads, in turn, to an augmented release of adenosine, which may activate A1R in afferent arterioles. By blocking those receptors, A1R antagonists cause an uncoupling of the tubuloglomerular feedback which may at least partly explain the elevated concentrations of adenosine measured in the urine of animals treated with SLV329. However, urinary excretion of paracrine mediators do not necessarily reflect their local tissue concentrations. Alternatively, blockade of A1R might result in elevated intracellular cyclic adenosine monophosphate levels and release in the kidney, which will eventually lead to increased extracellular adenosine concentrations due to cyclic adenosine monophosphate degradation. However, in spite of the observed increase in urinary adenosine excretion, Dasatinib SLV329 did not decrease the rate of creatinine clearance, even at the highest dose. Previous studies demonstrated that a single application of an A1R antagonist causes an increase of renal sodium and water excretion in animals and patients with liver cirrhosis without affecting the glomerular filtration rate. As a next step towards a possible clinical application, the present study investigated for the first time the effects of a chronic application of a selective A1R antagonist on kidney function and mortality starting at an early stage of liver cirrhosis. This proof-of-concept experiment included a low-dose furosemide-treated group because loop diuretics are often applied in cirrhotic patients and tend to deteriorate renal function. However, monotherapy with a loop diuretic is of course not the typical clinical situation at an early stage of liver cirrhosis without severe water retention. In the present study the creatinine clearance, used as a surrogate for the glomerular filtration rate, was significantly reduced in cirrhotic animals, especially in those receiving furosemide. In contrast, the A1R antagonist SLV329 was able to prevent this decline of creatinine clearance. The reduction of mortality in cirrhotic animals treated with SLV329 in comparison to vehicle treatment was not statistically significant. However, mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide. It is a limitation of this study that creatinine clearance was used instead of inulin clearance. Inulin clearance was not used because mortality would have increased further due to additional anesthesia. Creatinine clearance is influenced by muscle mass, liver function and tubular secretion of creatinine. However, there were no significant differences of neither body weight nor liver function between cirrhotic animals with and without SLV329 treatment. Tubular secretion of creatinine increases with declining glomerular filtration rate.