The investigation of mechanism of salt-sensitive hypertension in animal models and cardiac diastolic heart failure in hypertensive patients

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In the present study, we demonstrated the crucial role of eNOS uncoupling-induced vascular endothelial dysfunction in chronic kidney disease (CKD) and salt-sensitive hypertension using Dahl salt-sensitive hypertensive (DS) rats and eNOS knockout mice. Furthermore, in clinical study, we found that peripheral endothelial dysfunction, assessed by digital peripheral arterial tonometry, was significantly impaired in human cardiac diastolic heart failure (DHF) patients. Furthermore, blood BH4 levels tended to be decreased in DHF patients, indicating the involvement of eNOS uncoupling by BH4 downregulation in human DHF as well as DS rats.