Chronic kidney disease is associated with cognitive dysfunction and cardiovascular remodeling in aged male and female Sprague‐Dawley rats

Abstract

AbstractBackgroundCardiovascular diseases (CVD), including increased central arterial stiffness (CAS), accompany chronic kidney disease (CKD) development. An increase in pulse wave velocity (PWV), an index for CAS, is implicated in age‐associated changes in the brain and potentiates the development of CI in CVD and CKD in humans and animal models. The aim of this study was to determine whether inducing CKD accelerates the development of CI and CAS in aged male and female rats.MethodTen months‐old male and female Sprague‐Dawley rats were fed with 0.25% adenine diet to accelerate CKD (n = 10‐12; CKD‐male, CKD‐female) or regular diet (n = 8‐10; CNT‐male, CNT‐female) for 8weeks. Body weight (BW), blood pressure (BP), heart rate (HR), aortic‐PWV (aPWV), behavioral tests, blood urea nitrogen (BUN), creatinine and hematocrit were assessed at the endpoint. The anxiety‐like behavior was tested in open field test (OFT) and elevated plus maze (EPM). Morris water maze (MWM) and cross maze (CM) were used to test spatial memory. The data were analyzed using two‐way ANOVA.ResultCKD development in both sexes was accompanied by kidneys enlargement, increase in BUN and creatinine, and reduction in hematocrit. In CKD‐male the kidney function was more compromised with higher levels of BUN and creatinine vs. CKD‐female (Table 1). CKD‐male had lower BW and SBP vs. CNT‐male (Table 1). CKD induced a reduction in HR, increase in aPWV and aortic weight in both sexes vs. respective CNT‐groups (Figure 1). Both CKD‐male and CKD‐female demonstrated a tendency of increase in path length to find the hidden platform in MWM, e.g., both sexes had numerically impaired spatial memory. CKD‐male spent less time in the center of OFT, a measure of anxiety, and loss of spatial memory, with a reduction of spontaneous alternation task assessed by CM. CKD‐female exhibited higher level of anxiety spending less time in open arm of EPM vs. CNT‐female (Figure 2).ConclusionCKD development in old male and female Sprague‐Dawley rats was accompanied by an increase in CAS, cardiovascular remodeling, and cognitive dysfunction. In CKD, CI affected different cognitive domains in the old males than in the age‐matched females.Supported by NIA/NIH/IRP