A low RH signal detected by EndoPAT, consistent with endothelial dysfunction, was associated with higher AE rate during follow-up. L_RHI was an independent predictor of AE. Non-invasive assessment of peripheral vascular function may be useful for the identification of patients at risk for cardiac AEs.

Background-Endothelin (ET-1) is one of the most potent vasoconstrictors and plays a seminal role in the pathogenesis of atherosclerosis. The present study was designed to test the hypothesis that long-term treatment with an endothelin-A (ET A ) receptor antagonist improves coronary endothelial function in patients with early coronary atherosclerosis. Methods and Results-Forty-seven patients with multiple cardiovascular risk factors, nonobstructive coronary artery disease, and coronary endothelial dysfunction were randomized in a double-blind manner to either the ET A receptor antagonist atrasentan (10 mg) or placebo for 6 months. Coronary endothelium-dependent vasodilation was examined by infusing acetylcholine (10 Ϫ6 to 10 Ϫ4 mol/L) in the left anterior descending coronary artery. N

CED is independently associated with ED and plasma ADMA concentration in men with early coronary atherosclerosis. This study further supports the role of the endothelium in systemic vascular diseases and the role of ADMA in the systemic manifestations of endothelial dysfunction.

Abstract-Endothelin plays an important role in the pathogenesis of atherosclerosis. The aim of the study was to evaluate the safety and hemodynamic and metabolic responses to 6 months treatment with atrasentan, the selective endothelin-A receptor antagonist. Seventy-two patients with multiple cardiovascular risk factors and nonobstructive coronary artery disease on coronary angiogram were randomly assigned in a double-blind manner to atrasentan or placebo. Mean aortic blood pressure decreased from 92Ϯ10 to 80Ϯ10 mm Hg (PϽ0.001) in the atrasentan group and did not change in the placebo group (93Ϯ10 and 92Ϯ11 mm Hg; Pϭ0.84). The difference between the groups was significant (PϽ0.001). No effect on heart rate was observed. In a subgroup of patients not treated with angiotensin-converting enzyme inhibitor, creatinine level decreased in the atrasentan versus the placebo group (Pϭ0.011). Fasting glucose (Pϭ0.026), glycosylated hemoglobin level (Pϭ0.041), triglyceride l (Pϭ0.013), lipoprotein-A (Pϭ0.046), and uric acid levels (Pϭ0.048) decreased significantly in the atrasentan group compared with the placebo group. No progression of angiographic coronary disease was observed. The most common adverse effects with atrasentan were nasal stuffiness, headache, and edema. In conclusion, 6 months of treatment with atrasentan results in a reduction of blood pressure and improvement in glucose and lipid metabolism. These findings suggest the beneficial role of atrasentan in the treatment of hypertension and metabolic syndrome. Key Words: blood pressure Ⅲ hypertension Ⅲ metabolic syndrome Ⅲ endothelin Ⅲ endothelin-A receptor Ⅲ edema E ndothelin-1 (ET-1) is a potent vasoconstrictor contributing to the complex regulation of vascular tone. 1 Beyond the effect in promoting vasoconstriction, it has become evident that ET-1 plays a seminal role in the atherogenic process. 2 Moreover, cardiac risk factors cause an increase in endothelin level and impairment of endothelial vasodilator function, 3-7 which is considered an important phase in atherogenesis. 8 The actions of ET-1 are mediated via two distinct receptor subtypes, endothelin A (ET A ) and endothelin B (ET B ). Most of the ET-1-mediated pressor effect results from stimulation of the ET A receptor. The ET B receptor mediates pulmonary clearance 9 and reuptake of ET-1 by endothelial cells, 10 promotes production of NO, and prevent apoptosis. 11 Thus, the influence of the ET B receptor on arterial pressure regulation is more controversial.In animal studies, an ET-1 receptor antagonist treatment resulted in reduced arterial pressure, 12,13 prevention or even regression of structural renal lesions, 14,15 and improvement of insulin action with significant reduction of hyperglycemia. 16,17 To date, only acute effects of ET receptor blockade on renal function 18 and insulin resistance 19 have been investigated in humans. Clinical experience on the impact of medium-to long-term ET A receptor blockade on blood pressure, renal function, and metabolic markers in patients with early atheros...

Introduction-Circulating cells that express CD34 including hematopoietic progenitors and endothelial progenitor cells may have a role in the development and progression of atherosclerosis. Endothelial dysfunction is an early manifestation of atherosclerotic disease. The aim of this study was to evaluate the association between coronary endothelial dysfunction (CED) and circulating CD34+ subsets.