title: Renal effects of adenosine A1-receptor antagonists in congestive heart failure.
abstract: Renal function is a very important prognostic indicator in patients with congestive heart failure. While some of the prognostic importance of poor renal function is related to the worse physiology associated with it, there are suggestions that the dysfunction itself is detrimental. Recently, it has been shown that adenosine may mediate much kidney activity. In addition to vasoconstrictive and vasodilatory effects, adenosine is intrinsic to the tubuloglomerular feedback which occurs when an acute increase in sodium levels in the proximal tubule feeds back to decrease glomerular filtration. Adenosine works via both adenosine A1 and A2 receptors. A1-receptor antagonists decrease afferent arteriolar pressure, and increase urine flow and sodium excretion. Studies suggest that A1-receptor antagonists cause a diuretic effect not by a change in the renal haemodynamics, but by the inhibition of water and sodium reabsorption in tubular sites secondary to direct tubuloglomerular feedback. Less consistent has been the occasional finding of increased glomerular filtration rate despite the lack of improved renal plasma flow. Clinically important questions are: what role adenosine plays in causing the poor renal function associated with heart failure and what A1-receptor antagonists do in such situations? If an A1-receptor antagonist could cause diuresis while maintaining or improving glomerular filtration, it would be a useful adjunct in the treatment of severe heart failure. We evaluated the effects of the A1-receptor antagonist CVT-124 (BG-9719) in heart failure patients. CVT-124 increased sodium excretion without decreasing glomerular filtration rate. These data suggest that adenosine might be an important determinant of renal function in patients with heart failure.
authors.affiliation: Division of Cardiology, University of Maryland School of Medicine, Baltimore 21201, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Gottlieb
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology; D006439:Hemodynamics; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000502:physiology*; D011379:Prognosis; D058915:Purinergic P1 Receptor Antagonists; D012964:Sodium / Q000493:pharmacokinetics
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D012964:Sodium; D000241:Adenosine