Temporal evolution of endothelial dysfunction in a rat model of chronic heart failure

San Francisco Medical Center, University of California.

OBJECTIVES. The goal of this study was to investigate the evolution of endothelial dysfunction and plasma renin activity in a rat model of heart failure. BACKGROUND. Endothelial dysfunction has been demonstrated in heart failure and may play a significant role in this pathophysiologic process. Studies have also suggested a physiologic interaction between the renin-angiotensin system and endothelium-derived relaxing factor. However, the evolution of endothelial dysfunction and plasma renin activity in heart failure has not been studied to date. METHODS. Endothelium-dependent and -independent relaxations were studied at 1, 4 and 16 weeks after coronary artery ligation in a rat model of heart failure. Thoracic aortic rings were placed in isolated organ baths and acetylcholine and sodium nitroprusside concentration response curves were generated. Plasma renin activity was assessed at each time point. RESULTS. Aortic rings from rats with heart failure demonstrated no evidence of endothelial dysfunction at week 1, although progressive rightward shifts in the acetylcholine curves and decreasing maximal relaxation over time compared with findings in sham-operated control rats were evident at weeks 4 and 16. The sodium nitroprusside curves were not different between rats with heart failure and sham-operated rats. Plasma renin activity was elevated at week 1 and progressively increased through week 16, even though it correlated poorly with endothelial dysfunction. CONCLUSIONS. This study suggests that endothelial dysfunction in heart failure is a progressive time-dependent process that probably plays a minor role early in heart failure. Although plasma renin activity increased significantly in rats with heart failure, it was poorly predictive of endothelial dysfunction.

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