Abstract 16743: Hyperphosphatemia and Hypozincemia Aggravated Hypertension and Cardiac Dysfunction in SHR/NDmcr-cp, a Model of Metabolic Syndrome

Abstract

Background: It is known that metabolic syndrome affects cardiac function. Given that patients with diabetic nephropathy easily suffer from hyperphosphatemia and hypozincemia and obesity also induces higher phosphorus and lower zinc levels in plasma, we investigated whether the higher phosphorus and lower zinc levels in plasma affect cardiovascular system using SHR/NDmcr-cp, a rat model of metabolic syndrome. We also investigated the effects of antioxidant, N-acetyl-L-cysteine (NAC), on the development of cardiac dysfunction under the above conditions. Methods & Results: Male SHR/NDmcr-cp and control (WKY) rats were divided into 3 groups and were fed control diet (P 0.3% w/w, Zn 0.2% w/w) or a high-phosphorus and zinc-deficient (P 1.2 % w/w, Zn 0.0 % w/w) diet. The latter group was treated with either NAC (1.5 mg/g per day) or vehicle from 8 to 12 weeks of age (n = 6 or 8 for each group). The systolic blood pressure was increased by high-phosphate and zinc-deficient diet in both the SHR/NDmcr-cp and the WKY. NAC treatment improved these changes. The echocardiographic data elucidated that left ventricular (LV) systolic and diastolic function was markedly reduced in the SHR/NDmcr-cp by high-phosphate and zinc-deficient diet and only LV diastolic function was reduced in the WKY by the same diets. The high-phosphate and zinc-deficient diet significantly induced fibrosis of myocardium in the SHR/NDmcr-cp pathologically, and this change was improved by NAC. Treatment with NAC prevented diastolic dysfunction in WKY, but in SHR/NDmcr-cp it could only improve systolic function but did not recover diastolic function. Conclusion: Dietary high phosphorus and deficiency of zinc induced cardiac dysfunction in rats. Cardiac dysfunction resisted against the protective effects by NAC in the rat model of metabolic syndrome.