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Journal of atherosclerosis and thrombosis

Reduction of NO-mediated Relaxing Effects in the Thoracic Aorta in an Experimental Chronic Kidney Disease Mouse Model.


PMID 25740549

Abstract

Chronic kidney disease (CKD) is known to frequently cause cardiovascular events. However, it is unclear how renal dysfunction affects the vascular response. We herein studied the effects of renal dysfunction on the aortic behavior in adenine-fed mice, investigating mechanisms underlying the occurrence of cardiovascular events in CKD patients. Biochemical analyses of the plasma creatinine, blood urea nitrogen (BUN) and glucose levels and measurements of the blood pressure were performed using C57BL/6 mice fed with and without an adenine-containing diet. The relaxing effects of acetylcholine (ACh) or sodium nitropurusside (SNP) and effects of NO synthase (NOS) inhibitors on the contractions induced by phenylephrine (PE) were measured in endothelium-intact aortas obtained from both mice. The mice fed 0.25% adenine for four weeks showed greater plasma creatinine and BUN concentrations than the control mice, suggesting that adenine-fed mice are a useful CKD model. Furthermore, ACh relaxed the PE-stimulated, endothelium-intact aortas, the effect of which was less potent in the adenine-fed mice than in the control mice. In contrast, the degree of SNP-induced relaxation of the aortas was the same in the adenine-fed mice and control mice. The α1-adrenergic agonist, PE, induced more potent absolute tension of the endothelium-intact aortas in the CKD model mice than in the control mice, while the NOS inhibitors, N-nitro-L-arginine (LNA) and asymmetric dimethylarginine (ADMA) enhanced the contraction effects of PE in both mice. The findings of this study indicate that spontaneous and stimulated NO release from the endothelium is decreased in the CKD model mouse aorta. The NO-mediated correlation between renal and elastic arterial endothelial dysfunction is suggested to be a cause of cardiovascular events in patients with CKD.

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