RENAL HEMODYNAMIC-RESPONSES TO ADENOSINE IN ACUTE-RENAL-FAILURE

Renal vascular reactivity was studied in rats with acute renal failure (ARF) to investigate whether changes in sensitivity to the renal haemodynamic effects of adenosine can explain why adenosine plays a significant role in some but not all forms of ARF. Experiments involved rats with glycerol-induced ARF in which adenosine antagonists have been shown previously to have beneficial effects and rats with HgCl2-induced ARF which was not ameliorated by treatment with the selective A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.1 mg/kg). Close renal arterial injections of adenosine (0.1-10 mu g) or noradrenaline (0.003-0.1 mu g) produced falls in renal blood flow in rats with HgCl2-induced ARF which were not statistically different from controls. Adenosine evoked falls in renal blood flow in rats with glycerol-induced ARF which were significantly greater 16 and 48 h, but not 30 min after glycerol injection. The enhanced responsiveness to adenosine's renal constrictor effects was most pronounced 48 h following glycerol injection when, for example, a dose of 10 mu g produced a fall of 60 +/- (SEM) 5% (n = 8) in renal blood now in comparison to a fall of 27 +/- 5 % (n = 8) in controls. By contrast to the renal vascular response to adenosine, the falls in renal blood now induced by noradrenaline in rats 48 h following glycerol injection were not statistically different from the decreases in renal blood flow recorded in control animals. The results of this study show that ARF induced by glycerol, but not HgCl2, is associated with the development of a significant and selective increase in sensitivity to the renal constrictor actions of adenosine. Such changes in vascular responsiveness appear to occur relatively late in the development of ARF and are unlikely to contribute to the role adenosine plays in the initiation of glycerol-induced ARF.