title: Use of a hanging-weight system for isolated renal artery occlusion during ischemic preconditioning in mice.
abstract: Renal failure from ischemia contributes to morbidity and mortality. Ischemic preconditioning (IP) represents a powerful strategy for kidney protection, and recent advances in transgenic mice may help elucidate its molecular mechanisms. However, murine IP is technically challenging and experimental details significantly influence results. Thus we developed a novel model for renal IP using a hanging-weight system for isolated renal artery occlusion. In contrast to previous models, this technique eliminates the need for clamping the vascular pedicle (artery/vein). In fact, assessment of renal injury after different time periods of ischemia (10-60 min) revealed highly reproducible increases in plasma creatinine and potassium levels, while creatinine clearance, urinary flow and potassium/sodium excretion were significantly attenuated. Using different numbers of IP cycles, we found maximal protection with four cycles of 4 min of ischemia-reperfusion. In contrast, no significant renal protection was observed with IP of the vascular pedicle. To assess transcriptional responses in this model, we isolated RNA from preconditioned kidneys and found time-dependent induction of erythropoietin mRNA and plasma levels with IP. Taken together, this model provides highly reproducible renal injury and protection by IP, thus minimizing variability associated with previous techniques based on clamping of the renal pedicle. Further studies on renal ischemia/IP in mice may consider this technique.
authors.affiliation: Dept. of Pharmacology and Toxicology, Tübingen Univ. Hospital, Wilhelmstr. 56, D-72074 Tübingen, Germany.
authors.forename: Almut
authors.initials: A
authors.lastname: Grenz
authors.forename: Tobias
authors.initials: T
authors.lastname: Eckle
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Dan Yang
authors.initials: DY
authors.lastname: Huang
authors.forename: Manfred
authors.initials: M
authors.lastname: Wehrmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Köhle
authors.forename: Klaus
authors.initials: K
authors.lastname: Unertl
authors.forename: Hartmut
authors.initials: H
authors.lastname: Osswald
authors.forename: Holger K
authors.initials: HK
authors.lastname: Eltzschig
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003404:Creatinine / Q000097:blood; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning / Q000295:instrumentation* / Q000379:methods*; D007668:Kidney / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D011188:Potassium / Q000097:blood / Q000652:urine; D012333:RNA, Messenger / Q000096:biosynthesis; D012077:Renal Artery / Q000502:physiology*; D012079:Renal Circulation / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D003404:Creatinine; D009195:Peroxidase; D011188:Potassium