© 2008 European Society of Cardiology
Adenosine and kidney function: Potential implications in patients with heart failure
Departments of Medicine and Pharmacology, University of California San Diego & VASDHCS San Diego, CA, USA
* Corresponding author. Departments of Medicine and Pharmacology, University of California San Diego & VA San Diego Healthcare System, 3350 La Jolla Village Drive (9151), San Diego, CA 92161, USA. Tel.: +1 858 552 8585x5945; fax: +1 858 642 438. E-mail address: vvallon{at}ucsd.edu (V. Vallon).
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Abstract |
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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 A1 receptor (A1R) antagonists as treatment for decompensated heart failure. A1R antagonists induce a eukaliuretic natriuresis and diuresis by blocking A1R-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 A1R in the preglomerular arteriole, so blocking A1R allows natriuresis to proceed while GFR remains constant or increases. The influence of A1R over vascular resistance in the kidney is augmented by angiotensin II while A1R activation directly suppresses renin secretion. These interactions could modulate the overall impact of A1R blockade on kidney function in patients taking angiotensin II blockers. A1R 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 A1R blockade could protect against renal ischaemia, A1R blockade may act on non-resident cells to exacerbate reperfusion injury, where ischaemia to occur. Despite these uncertainties, the available data on A1R antagonist therapy in patients with decompensated heart failure are promising and warrant confirmation in further studies.
Key Words: Adenosine • Kidney • Heart failure • Tubuloglomerular feedback • Reabsorption • Angiotensin II
Received September 28, 2007; Revised January 7, 2008; Accepted January 15, 2008
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