Central Role for Marinobufagenin in the Pathogenesis of Uremic Cardiomyopathy
Abstract (Summary)Patients with chronic renal failure develop a “uremic” cardiomyopathy characterized by diastolic dysfunction, cardiac hypertrophy and systemic oxidant stress. Patients with chronic renal failure also are known to have increases in the circulating concentrations of the cardiotonic steroid marinobufagenin. On this background, we hypothesized that elevations in circulating marinobufagenin may be involved in the cardiomyopathy. First, we observed that administration of marinobufagenin (10 ?g/kg/day) for 4 weeks caused comparable increases in plasma MBG as partial nephrectomy at 4 weeks. Marinobufagenin infusion caused increases in conscious blood pressure, cardiac weight and the time constant for left ventricular relaxation similar to partial nephrectomy. Decreases in the expression of the cardiac sarcoplasmic reticulum ATPase, cardiac fibrosis and systemic oxidant stress were observed with both marinobufagenin infusion and partial nephrectomy. Next, rats were actively immunized against a marinobufagenin -bovine serum albumin conjugate or bovine serum albumin control, and partial nephrectomy was subsequently performed. Immunization against marinobufagenin attenuated the cardiac hypertrophy, impairment of diastolic function, cardiac fibrosis and systemic oxidant stress seen with partial nephrectomy without significant effect on conscious blood pressure. These data suggest that the increased concentrations of marinobufagenin are important in the cardiac disease and oxidant stress state seen with renal failure.
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:marinobufagenin fibrosis cardiac flt 1
Date of Publication:01/01/2008