title: Adenosine A1 receptors in contrast media-induced renal dysfunction in the normal rat.
abstract: Renal vasoconstriction with resultant tissue hypoxia, especially in the renal medulla, has been suggested to play a role in contrast media (CM)-induced nephropathy. In this study we investigated the effects of injection of the non-ionic low-osmolar CM iopromide with and without pretreatment with the selective adenosine A1-receptor antagonist DPCPX. The effects were evaluated on regional renal blood flow, outer medullary oxygen tension (PO2) and urine output in normal anaesthetised rats. A laser-Doppler technique was used for recording haemodynamic changes while oxygen microelectrodes were used for oxygen measurements. The A1-receptor antagonist per se elevated glomerular filtration rate (+44%), cortical blood flow (+15%) and urine output (threefold) while reducing outer medullary PO2 (-24%). Administration of CM reduced outer medullary blood flow (OMBF; -26%) and PO2 (-80%) but did not affect cortical blood flow. Urine output increased 28-fold by CM while arterial blood pressure was reduced. The CM-mediated effect on haemodynamics, PO2, urine output and blood pressure was unaffected by the A1-receptor antagonist. Adenosine A1-receptors are not important mediators of the depression of outer medullary blood flow and PO2 caused by the CM iopromide in the normal rat; however, A1-receptors are tonically active to regulate renal haemodynamics, PO2 and urine production during normal physiological conditions.
authors.affiliation: Department of Diagnostic Radiology, University Hospital, 75185 Uppsala, Sweden. per.liss@rtg.uas.lul.se
authors.forename: Per
authors.initials: P
authors.lastname: Liss
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Carlsson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Palm
authors.forename: Peter
authors.initials: P
authors.lastname: Hansell
mesh_terms: D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003287:Contrast Media / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007472:Iohexol / Q000031:analogs & derivatives* / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D007672:Kidney Cortex / Q000098:blood supply; D007679:Kidney Medulla / Q000098:blood supply / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D008297:Male; D008839:Microelectrodes; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D014556:Urine; D014970:Xanthines / Q000494:pharmacology*
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D003287:Contrast Media; D014970:Xanthines; D007472:Iohexol; C038192:iopromide; C051360:1,3-dipropyl-8-cyclopentylxanthine; D010100:Oxygen