Abstract
Experimental models of cardiovascular diseases largely depend on the genetic background. Subtotal 5/6 nephrectomy (5/6 Nx) is the most frequently used model of chronic kidney disease (CKD) in rodents. However, in mice, cardiovascular consequences of 5/6 Nx are rarely reported in details and comparative results between strains are scarce. The present study detailed and compared the outcomes of 5/6 Nx in the 2 main strains of mice used in cardiovascular and kidney research, 129/Sv and C57BL/6JRj. Twelve weeks after 5/6 Nx, CKD was demonstrated by a significant increase in plasma creatinine in both 129/Sv and C57BL/6JRj male mice. Polyuria and kidney histological lesions were more pronounced in 129/Sv than in C57BL/6JRj mice. Increase in albuminuria was significant in 129/Sv but not in C57BL/6JRj mice. Both strains exhibited an increase in systolic blood pressure after 8 weeks associated with decreases in cardiac systolic and diastolic function. Heart weight increased significantly only in 129/Sv mice. Endothelium-dependent mesenteric artery relaxation to acetylcholine was altered after 5/6 Nx in C57BL/6JRj mice. Marked reduction of endothelium-dependent vasodilation to increased intraluminal flow was demonstrated in both strains after 5/6 Nx. Cardiovascular and kidney consequences of 5/6 Nx were more pronounced in 129/Sv than in C57BL/6JRj mice.
Highlights
Chronic kidney disease (CKD) is a major health problem, with a worldwide prevalence of 13%1
Different models of chronic kidney disease (CKD) have been developed in rodents, including kidney mass reduction by 5/6 nephrectomy (5/6 Nx), DOCA salt nephropathy, unilateral ureteral obstruction, oxalate-induced CKD, adenine-induced CKD and genetic mutation of Col4A38–12, but these models do not fully reproduce the CV consequences of CKD observed in humans, including coronary heart disease. 5/6 Nx has been widely used in rats[13,14] because of the persistent decrease in glomerular filtration rate (GFR), proteinuria, glomerular sclerosis and hypertension induced, contributing to the major interest of this model[15]
The precise cardiovascular consequences of the 5/6 Nx model are poorly defined in mice, because of methodological differences between studies (Table 2)
Summary
Chronic kidney disease (CKD) is a major health problem, with a worldwide prevalence of 13%1. Several factors, including surgical difficulties, have limited the use of 5/6 Nx in mice[16] This is of critical importance in particular because transgenic mice, most commonly developed on a C57BL/6JRj background, currently represent a key experimental tool. Irrespective of the genetic background, renal, cardiac and vascular consequences of 5/6 Nx in mice are generally the subject of focused studies, and their occurrence and severity are poorly characterized together. In this context, the aim of this study is to comparatively describe the consequences of 5/6 Nx in the two commonly used mouse strains C57BL/6JRj and 129/Sv, with a specific focus on structural and functional disorders of the cardiovascular system
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