Effect of Exercise on Cardiac Tissue Oxidative and Inflammatory Mediators in Chronic Kidney Disease

Abstract

Background: Chronic renal failure (CRF) results in diminished physical activity and increased risk of cardiovascular disease (CVD). CVD risk factors are raised by sedentary life style and ameliorated by physical fitness in the general population. Accordingly, exercise improves hypertension, endothelial dysfunction, insulin resistance, dyslipidemia, inflammation and oxidative stress in high-risk populations. This study was designed to explore the effect of exercise on oxidative and inflammatory mediators in the left ventricle (LV) of CRF rats. Methods and Results: One week after 5/6 nephrectomy female rats were housed in either regular cages or cages equipped with running wheels for 4 weeks. Sham-operated rats housed in regular cages served as controls. Sedentary CRF rats exhibited azotemia, hypertension, anemia, oxidative stress, activation of NF-κB and upregulations of reactive oxygen species-generating enzyme, NAD(P)H oxidase, MCP-1, cyclooxygenase-2 (COX-2), and PAI-1 in LV. The CRF rats assigned to the exercise group ran 6.8 ± 0.7 km/day and 72 ± 8 min/day. Voluntary exercise reversed NF-κB activation and lowered NAD(P)H oxidase, PAI-1, MCP-1 and COX-2 abundance, increased LV mass by raising myofibrillar proteins and ameliorated anemia without affecting renal function or arterial pressure. Conclusions: CRF resulted in upregulation of prooxidant/proinflammatory pathways in LV. These changes were ameliorated by exercise, which indicates the potential cardiovascular benefit of exercise in renal insufficiency.

Reactive oxygen species and vascular biology: implications in human hypertension

“…In experimental models of hypertension and in patients with coronary artery disease, exercise reduced vascular NAD(P)H oxidase activity and ROS production, ameliorated vascular injury and reduced blood pressure. 188,189 CONCLUSIONS Extensive data confirm the importance of ROS in the physiological control of vascular function, through regulation of endothelial function and vascular tone via tightly controlled redox-sensitive signaling pathways. Uncontrolled production/degradation of ROS results in oxidative stress, which induces cardiovascular, renal and neural damage with associated increase in blood pressure.…”

The Cardiovascular Effect of the Uremic Solute Indole-3 Acetic Acid

“…Studies support the notion that the COX-2/PGE2 axis has an important role in atherosclerosis. [28][29][30] In animal models of CKD, COX-2 is upregulated 31,32 and associated with a proinflammatory and prooxidant profile. 31,32 Serum from patients with CKD increases COX-2 expression in smooth muscle cells 33 and induces endothelial p38 MAPK and NF-kB activation.…”

“…[28][29][30] In animal models of CKD, COX-2 is upregulated 31,32 and associated with a proinflammatory and prooxidant profile. 31,32 Serum from patients with CKD increases COX-2 expression in smooth muscle cells 33 and induces endothelial p38 MAPK and NF-kB activation. 34 In our cultured endothelial cells, IAA increased COX-2 level and PGE2 production, induced NF-kB activation, and increased oxidative stress, mimicking the inflammatory and prooxidative profile found in CKD.…”

Effects of aerobic exercise training in animal models of hypertension.

“…(61) However, the APT associated with enalapril or losartan reduced the BP and induced significant additional protection against an increase in glomerular sclerosis. (61) runs on voluntary racing TFA did not induce BP normalization in Wistar rats (62,63) or Sprangue-Dawley rats subjected to 5/6 nephrectomy, although reducing oxidative stress in heart tissue (64) to improve vascular function.…”