Relationship between renal injury and vascular function in rats exposed to renal ischemia/reperfusion

[Speaker] Keisuke Nakagawa:1
[Co-author] Masaya Kanada:1, Masahide Donouchi:1, Ryosuke Tanaka:1, Mamoru Ohkita:1, Yasuo Matsumura:1
1:Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Japan

Background: Ischemia/reperfusion (IR) injury is a leading cause of acute kidney injury (AKI), which is frequent clinical syndrome with high morbidity and mortality. AKI results in renal tissue injury and renal dysfunction. In addition, AKI leads to failure of multiple organs such as brain, heart and lung. Furthermore, it is well known that the vascular dysfunction occurs in the renal arteries and microvessels following IR, but there are few reports on vascular reactivity in large vessels such as the thoracic aorta. In this study, we examined time-dependent changes of renal function in ischemic AKI (IAKI) model rats. At the same time, we investigated the correlative relationship between endothelium-dependent vasorelaxant responses to acetylcholine (Ach) of the thoracic aorta and renal function after IR.
Methods: Male SD rats of 8 weeks of age were used. Two weeks after the right nephrectomy, the IAKI model (IR group) was prepared by occluding the blood flow of the left renal artery and vein for 45 minutes and reperfusion. 1, 7 and 28 days after IR treatment were designated as IR-1, IR-7 and IR-28 groups, respectively. Blood and urine were collected and renal function parameters (blood urea nitrogen, plasma creatinine, creatinine clearance) were measured. Endothelium-dependent vasorelaxation of thoracic aorta was assessed by organ chamber technique.
Results: Renal function was significantly reduced in IR-1 group compared with sham group, but the sensitivity of endothelium-dependent vasorelaxant responses to Ach increased. In the IR-7 and IR-28 group, although renal function recovered to the same extent as sham group, the sensitivity of endothelium-dependent vasorelaxant responses was significantly attenuated as compared with sham group. Furthermore, this attenuation was more prominent in IR-28 group.
Conclusions: Renal function was time-dependently restored after IR, but the sensitivity of thoracic aorta to Ach was significantly attenuated. Taken together, these results suggest that the attenuation of endothelium-dependent vasorelaxation occurs irrespective of the recovery process in renal function after IR. Thus, unknown factors seem to induce vascular abnormality of IAKI rats.

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