Hypertension is more prevalent in blacks than whites, and the reasons for this difference remain unclear. To test whether endothelin may play a role in these racial variations, we analyzed plasma samples from black and white women and men with high blood pressure by an enzyme-linked immunoassay specific for endothelin-1 (ET-1), a potent vasoconstrictor, and compared them with those obtained from similar subjects with normal blood pressure. Both female and male hypertensive blacks had elevated levels of immunoreactive ET-1 (11.3 +/- 1.0 and 12.3 +/- 1.3 pmol/L, respectively) compared with values in normotensive control blacks (1.5 +/- 0.2 and 1.4 +/- 0.2 pmol/L). Corresponding values in female and male hypertensive whites were 3.8 +/- 0.6 and 3.8 +/- 0.6 pmol/L, respectively, compared with respective values of 1.4 +/- 0.1 and 2.8 +/- 0.4 pmol/L in normotensive control whites. These results indicate that plasma concentrations of immunoreactive ET-1 levels differ significantly between black and white individuals with high blood pressure. This finding may be an important factor in the etiology of racial differences in the prevalence and severity of hypertension and deserves further study [corrected].

While systemic plasma endothelin-1 (ET-1) levels are increased during acute crisis in sickle cell disease, the relative levels of potent vasoactive factors that contribute to the regulation of vascular function, such as ET-1, NO, and cell-free hemoglobin, during the course of periodic vaso-occlusive episodes remain unclear. Moreover, whether and to what extent sickling-induced release of ET-1 alters vascular tone is not completely understood. To investigate the sequential changes in circulating vasoactive factors, we measured plasma ET-1, NO metabolites (NOx), and cell-free hemoglobin (Hb) before (steady-state), during (crisis), and after a vaso-occlusive (post-crisis) episode. Steadystate ET-1 levels (fmol/mL) increased from 2.3 ± 0.4 to 11.0 ± 1.4 and 4.2 ± 1.0 during crisis and post-crisis periods, respectively. There was no significant difference in plasma NOx levels. Cell-free Hb levels were significantly higher in sickle cell patients in all phases as compared to the control group, and especially during crisis cell-free Hb levels were elevated by 4-fold (209,000 ± 31,000 vs. 46,000 ± 5,300 ng/mL in steady-state). Conditioned medium from human pulmonary artery endothelial cells exposed to sickled erythrocytes prepared by deoxygenation induced contraction of aortic rings, and this effect was blocked by an ET A receptor antagonist. These findings indicate that ET-1 is the predominant contractile factor released by cultured endothelial cells upon exposure to deoxygenated sickled SS erythrocytes and ET-1-NO-NO scavenger balance is altered in favor of vasoconstriction during an acute episode in SCD. Am.

Plasma concentrations of immunoreactive endothelin-1 (irET-1) are significantly elevated in blacks with hypertension. In the present study, we investigated the effect of the regulation of high blood pressure on plasma irET-1 levels in black hypertensive individuals. After the initial blood samples were collected from 20 black patients with uncontrolled high blood pressure (Day 1), an intensive antihypertensive treatment was initiated, and the blood pressure and plasma irET-1 levels were monitored on days 2, 8, and 22. When the high blood pressure was brought under control with commonly used antihypertensive medications, plasma irET-1 concentrations dropped dramatically, suggesting that ET-1 concentrations rise as a consequence of high blood pressure in this study group.

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