title: Adenosine A2 receptor-mediated regulation of renal hemodynamics and glomerular filtration rate is abolished in diabetes.
abstract: Alterations in glomerular filtration rate (GFR) are one of the earliest indications of altered kidney function in diabetes. Adenosine regulates GFR through tubuloglomerular feedback mechanism acting on adenosine A1 receptor. In addition, adenosine can directly regulate vascular tone by acting on A1 and A2 receptors expressed in afferent and efferent arterioles. Opposite to A1 receptors, A2 receptors mediate vasorelaxation. This study investigates the involvement of adenosine A2 receptors in regulation of renal blood flow (RBF) and GFR in control and diabetic kidneys. GFR was measured by inulin clearance and RBF by a transonic flow probe placed around the renal artery. Measurements were performed in isoflurane-anesthetized normoglycemic and alloxan-diabetic C57BL/6 mice during baseline and after acute administration of 3,7-dimethyl-1-propargylxanthine (DMPX), a selective A2 receptor antagonist. GFR and RBF were lower in diabetic mice compared to control (258 ± 61 vs. 443 ± 33 μl min(-1) and 1,083 ± 51 vs. 1,405 ± 78 μl min(-1)). In control animals, DMPX decreased RBF by -6%, whereas GFR increased +44%. DMPX had no effects on GFR and RBF in diabetic mice. Sodium excretion increased in diabetic mice after A2 receptor blockade (+78%). In conclusion, adenosine acting on A2 receptors mediates an efferent arteriolar dilatation which reduces filtration fraction (FF) and maintains GFR within normal range in normoglycemic mice. However, this regulation is absent in diabetic mice, which may contribute to reduced oxygen availability in the diabetic kidney.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, BMC, 571, 75123, Uppsala, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Persson
authors.affiliation: Department of Medical Cell Biology, Uppsala University, BMC, 571, 75123, Uppsala, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Hansell
authors.affiliation: Department of Medical Cell Biology, Uppsala University, BMC, 571, 75123, Uppsala, Sweden. fredrik.palm@mcb.uu.se.|Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. fredrik.palm@mcb.uu.se.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Palm
mesh_terms: D000241:Adenosine / Q000378:metabolism; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000378:metabolism / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D005919:Glomerular Filtration Rate; D006439:Hemodynamics / Q000502:physiology*; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D043683:Receptors, Adenosine A2 / Q000737:chemistry / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D043683:Receptors, Adenosine A2; C057837:3,7-dimethyl-1-propargylxanthine; D000241:Adenosine; D013805:Theobromine