Role of adenosine in renal protection induced by a brief episode of ischemic preconditioning in rats.
The protective effect of a brief episode of ischemic preconditioning was examined at an early phase of ischemic-reperfusion injury in the rat kidney. Rats were subjected to 50 min of left renal artery occlusion followed by 120 min of reperfusion. Ischemic preconditioned rats were subjected to preconditioning with two cycles of 3-min ischemia and 5-min reperfusion (IPC). Ischemic-reperfusion injury led to a low recovery of the glomerular filtration rate (GFR). Overt morphological changes, consisting of blood trapping and tubular collapse, were seen. IPC improved the recovery of GFR and renal morphology. The IPC effect was not blocked by 8-(p-sulfophenyl)-theophylline (SPT), a non-selective adenosine receptor antagonist, by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective A1-receptor antagonist, or by 3,7-dimethyl-1-propargylxanthine (DMPX), a selective A2-receptor antagonist. Intravenous infusion of adenosine (30 microg/min per rat, for 5 min) prior to the 50-min occlusion improved the recovery of GFR, and this protection of GFR was blocked by SPT. Thus, both IPC and exogenous adenosine attenuated ischemic-reperfusion injury of the kidney. However, because three adenosine receptor antagonists failed to abolish the protective effect of IPC, there is no evidence to indicate that activation of adenosine receptors contributes to the IPC effect in the kidney.
Sugino
H
H
Division of Pathophysiology, Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. suginoh@platinum.pharm.kitasato-u.ac.jp
Shimada
H
H
Tsuchimoto
K
K
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007511:Ischemia / Q000209:etiology / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D007668:Kidney / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012078:Renal Artery Obstruction / Q000150:complications; D012079:Renal Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D018617:Ultrasonography, Doppler, Pulsed; D014970:Xanthines / Q000494:pharmacology
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C057837:3,7-dimethyl-1-propargylxanthine; C031433:8-(4-sulfophenyl)theophylline; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; D000241:Adenosine; D013805:Theobromine