Contribution of volume overload to progression of cardiovascular disease in a rat model of chronic kidney disease

Abstract

Volume overload is a common phenomenon in patients with chronic kidney disease that is associated with cardiovascular risk factors. However, its contribution to the development of adverse cardiovascular outcomes in those patients is not fully understood. Thus, the present work investigated the effect of salt-induced volume overload on cardiac functions and geometry in a rat model of chronic kidney disease. Thirty adult male Sprague-Dawley rats were randomly divided. One set of animals received a sham operation, while another set of animals underwent uninephrectomy. Rats were then fed either a normal-salt (0.4%) or high-salt (8.0%) diet for 6 weeks. The salt-loaded, uninephrectomized rats were treated with indapamide (3 mg·kg·day, orally) for 6 weeks. We found that uninephrectomized rats subjected to a high-salt diet (8.0%) for 6 weeks presented with hypertension, proteinuria, decreased renal Klotho expression, and deterioration in cardiac hemodynamics and histology. Echocardiography to assess cardiac function showed that ejection fraction and fractional shortening were positively correlated with relative renal Klotho expression. In conclusion, salt-induced volume overload in a rat model of chronic kidney disease has an adverse cardiovascular outcome and is associated with inflammatory activation and decrease in renal Klotho expression.

Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats

“…However, little is known about the development of animal models for CKD-PH. Classic rodent models, such as 5/6 nephrectomy-induced CKD 23 , adenine-induced CKD 26 , high-salt diet-induced CKD 27 , and 5/6 nephrectomy and high-salt diet-induced CKD 28 , have been frequently used in earlier study. Moreover, activation of the RAAS system has been shown to lead to high blood pressure and cardiac remodeling (myocardial hypertrophy and fibrosis) in CKD patients and animal models [29][30][31][32][33] .…”