Role of endothelin-1 in genesis of coronary artery disease.

BACKGROUND: The endothelial cells produce the most potent vasoconstrictor known as endothelin-1. Elevated plasma levels of endothelin have been associated with coronary artery disease, essential hypertension and heart failure. The aims of the present study were, to compare the plasma endothelin-1 levels in coronary artery disease patients and healthy controls, to confirm endothelin-1 as surrogate marker for coronary artery disease and to compare the presence of endothelin-1 like immunoreactivity in aortic and internal mammary artery specimens obtained during coronary artery bypass graft surgery. METHODS AND RESULTS: The circulating levels of endothelin-1 were determined by enzyme-linked immunoassay in patients of coronary artery disease (n=145) and compared with healthy controls (n=70). Tissue endothelin-1 immunoreactivity was examined by immunohistochemical method in aortic and internal mammary artery tissue specimens obtained from 20 patients of coronary artery disease during coronary artery bypass grafting to understand the role of endothelin in atherosclerosis. Significantly higher levels (p < 0.001) of endothelin-1 were observed in all patients of coronary artery disease as compared to healthy controls. The immunoreactivity of endothelin-1 was localized to endothelial cell layer in internal mammary artery whereas in aortic specimens, in addition to endothelial cell layer, immunoreactivity was seen in the cytoplasm of smooth muscle cells of intima and media. CONCLUSIONS: The significant increase in plasma endothelin-1 in coronary artery disease cases as compared to healthy subjects and presence of tissue endothelin-1 immunoreactivity in smooth muscle cells of intimal as well as medial layers of aorta confirms the role of endothelin-1 as a surrogate marker of atherosclerosis.

Role of endothelial cell dysfunction in essential hypertension.

BACKGROUND: Hypertension is associated with functional and morphological alterations of the endothelium, which disturbs delicate balance of endothelium-derived factors resulting in endothelial dysfunction. The endothelial dysfunction could then facilitate the maintenance of elevated peripheral resistance, which would favor the occurrence of atherosclerosis. AIMS AND OBJECTIVES: The aim of the present study was to determine the circulating levels of vasodilators [nitric oxide (NO) and prostacyclin (PGI2)] and vasoconstrictors [endothelin I (ET-I) and thromboxane (TX)A2)], which reflect endothelial cell dysfunction. METHOD: Nitric oxide as nitrites and nitrates (NOx) were measured spectrophotometrically; ET-I, TXA2 (as TXB2) and PGI2 (as 6 keto PGFIalpha) were measured using enzyme immunoassay methods in 54 male subjects having predominantly untreated, mild hypertension and compared with age-matched 75 healthy controls. RESULTS: Significantly higher levels of ET-I (p<0.001) and TXB2 (p<0.001) were found in essential hypertension subjects (EHT) as compared to controls. No significant difference was observed in NOx and 6 keto PGFIalpha between the two groups. There was significant increase (p = 0.005) in the ratio of TXB2/6 keto PGFIalpha in EHT subjects as compared to controls. CONCLUSIONS: Elevated levels of vasoconstrictors in untreated essential hypertension subjects as compared to controls confirmed the presence of endothelial dysfunction, even in mild cases of hypertension. Early detection of endothelial dysfunction may be a useful measure to guide therapy before the damaging effects of hypertension manifests.