Adenosine and kidney function: potential implications in patients with heart failure.
Therapy of heart failure is more difficult when renal function is impaired. Here, we outline the effects on kidney function of the autacoid, adenosine, which forms the basis for adenosine A(1) receptor (A(1)R) antagonists as treatment for decompensated heart failure. A(1)R antagonists induce a eukaliuretic natriuresis and diuresis by blocking A(1)R-mediated NaCl reabsorption in the proximal tubule and the collecting duct. Normally, suppressing proximal reabsorption will lower glomerular filtration rate (GFR) through the tubuloglomerular feedback mechanism (TGF). But the TGF response, itself, is mediated by A(1)R in the preglomerular arteriole, so blocking A(1)R allows natriuresis to proceed while GFR remains constant or increases. The influence of A(1)R over vascular resistance in the kidney is augmented by angiotensin II while A(1)R activation directly suppresses renin secretion. These interactions could modulate the overall impact of A(1)R blockade on kidney function in patients taking angiotensin II blockers. A(1)R blockers may increase the energy utilized for transport in the semi-hypoxic medullary thick ascending limb, an effect that could be prevented with loop diuretics. Finally, while the vasodilatory effect of A(1)R blockade could protect against renal ischaemia, A(1)R blockade may act on non-resident cells to exacerbate reperfusion injury, where ischaemia to occur. Despite these uncertainties, the available data on A(1)R antagonist therapy in patients with decompensated heart failure are promising and warrant confirmation in further studies.
Vallon
Volker
V
Departments of Medicine and Pharmacology, University of California San Diego & VASDHCS, San Diego, CA 92161, USA. vvallon@ucsd.edu
Miracle
Cindy
C
Thomson
Scott
S
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007685:Kidney Tubules, Collecting / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000503:physiopathology; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D015427:Reperfusion Injury / Q000503:physiopathology; D014661:Vasoconstriction / Q000502:physiology; D014667:Vasopressins / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology
C097280:1,3-dipropyl-8-(2-(5,6-epoxy)norbornyl)xanthine; D018047:Receptors, Purinergic P1; D014970:Xanthines; D014667:Vasopressins; D000241:Adenosine