Role of adenosine in the renal responses to contrast medium

Despite the development of non-ionic radiographic contrast media (CM), CM-induced nephropathy is a clinically important problem in patients with pre-existing renal insufficiency. We examined the effects of non-ionic CM (iohexol) on renal function in conscious dogs with and without renal insufficiency, and evaluated the effects of a non-selective (theophylline), an A1 selective (KW-3902), and an A2 selective adenosine antagonist (KF17837) on the renal responses to CM. In sham-operated group, iohexol (2 ml/kg/min for 3 min) increased effective renal plasma flow (ERPF) and glomerular filtration rate (GFR), whereas in renal insufficiency group (with subtotal nephrectomy), following transient increases in ERPF and GFR, CM markedly decreased ERPF (-46.5 ± 6.7%) and GFR (-51.2 ± 7.1%). In sham-operated group, theophylline and KF17837 markedly attenuated CM-induced increases in ERPF and GFR, while KW-3902 had no effects on CM-induced increases in ERPF or GFR. In renal insufficiency group, initial increases in ERPF and GFR were blunted by theophylline and KF17837. In contrast, the subsequent decreases in ERPF and GFR were attenuated by theophylline (%ΔERPF, -12.2 ± 3.2% vs. -46.6 ± 6.7%, P < 0.01; %ΔGFR, 4.3 ± 2.5% vs. -51.0 ± 7.1%, P < 0.01), and were completely prevented by KW-3902 (%ΔERPF, 10.8 ± 2.9%; %ΔGFR, 23.8 ± 4.4%), whereas KF17837 aggravated ERPF (-73.3 ± 5.3%) and GFR (-78.4 ± 5.3%). These data indicate that in normal renal function, iohexol elicits renal vasodilation by activating mainly the adenosine A2 receptors. In contrast, in impaired renal function, CM induces both A2 and A1 activation; the former is associated with the initial renal vasodilation, while the latter is responsible for the sustained aggravation of renal hemodynamics.