Contrast media can induce both a decrease in renal blood flow and a reduction in glomerular filtration rate (GFR) when administered to both experimental animals and humans. In the present study we have examined the role of adenosine in mediating these effects using the isolated perfused rat kidney. Kidneys were perfused with a 6.7%-(w/v)-albumin-based perfusate supplemented with glucose and amino acids ( n = 6 per group). They were exposed to diatrizoate [20 mg of iodine (mgI)/ml; osmolality 1650 mOsm/kg of water] or iotrolan (20 mgI/ml; osmolality 320 mOsm/kg of water) in the presence or absence of theophylline (10.8 µ g/ml), or to diatrizoate in the presence or absence of a specific adenosine A 1 receptor antagonist (KW-3902; 2 µ g/ml) or a specific A 2 receptor antagonist (KF17837; 6 µ g/ml). Diatrizoate ( n = 6) produced a fall in GFR from 0.65±0.04 to 0.42±0.03 ml·min -1 ·g -1 ( P < 0.05); renal perfusate flow (RPF) also declined, from 36.5±3.8 to 22.0±3.2 ml·min -1 ·g -1 ( P < 0.05). Iotrolan ( n = 6) produced a fall in GFR from 0.64±0.02 to 0.48±0.04 ml·min -1 ·g -1 ( P < 0.05) and in RPF from 33.3±3.8 to 24.0±3.0 ml·min -1 ·g -1 ( P < 0.05). Theophylline (10.8 µ g/ml) prevented the fall in GFR caused by either diatrizoate (baseline, 0.63±0.05 ml·min -1 ·g -1 ; diatrizoate+theophylline, 0.60±0.04 ml·min -1 ·g -1 ) or iotrolan (basline, 0.64±0.04 ml·min -1 ·g -1 ; iotrolan+theophylline, 0.67±0.05 ml·min -1 ·g -1 ), but did not affect the decreases in RPF caused by either agent. KW-3902 (2 µ g/ml) also prevented the fall in GFR produced by diatrizoate (baseline, 0.66±0.05 ml·min -1 ·g -1 ; diatrizoate+KW-3902, 0.61±0.05 ml·min -1 ·g -1 ), while the fall in RPF remained unaffected. KF17837 (6 µ g/ml) had no effect on the decreases in either GFR or RPF induced by diatrizoate ( n = 6 per group). The results suggest a role for adenosine acting at the A 1 receptor in mediating the decrease in GFR induced by contrast media. This effect is independent of a change in renal vascular resistance, and possibly secondary to mesangial cell contraction causing a decrease in the ultrafiltration coefficient.

1. We studied the effects of the non-selective, non-peptide, orally active endothelin (ET) receptor antagonist bosentan (Ro 47–0203) on rat hepatic and mesenteric vascular membrane 125 I-ET-1 binding characteristics in vitro and ex vivo (after bosentan by gavage in vivo ). 2. Bosentan caused a concentration-dependent competitive inhibition of 125 I-ET-1 binding to female rat mesenteric vascular (predominantly ETA receptors) and hepatic (predominantly ETB receptors) membranes in vitro and ex viva 3. The time course of the inhibition of binding ex vivo after administration of bosentan in vivo was 1–4 h for mesenteric vascular (predominantly ETA receptors) binding and 1–16 h for hepatic (predominantly ETB receptors) binding. 4. The time course of displacement of 125 I-ET-1 binding from mesenteric vascular and hepatic membranes by bosentan in vitro was similar. 5. Since bosentan is significantly excreted by the liver, the prolonged hepatic 125 I-ET-1 binding by bosentan presumably represents hepatic accumulation of bosentan, which may have implications for bosentan antagonizing the actions of ET in the liver.

1. A Workshop on α-Adrenoceptors was held at Loch Lomond, Scotland in July 1984. Forty participants from different disciplines in the pharmacological, biochemical, physiological and clinical fields considered the questions: (i) How many subtypes of α-receptor do we need at present? (ii) What are the activation steps set in motion by α-adrenoceptors? (iii) What are the physiological roles of α-adrenoceptors in circulatory control? (iv) What are the pathophysiological roles and how can α-receptors be manipulated in disease? 2. This paper reviews the major points which arose and is intended as a guide to the papers in this Supplement.