Ethnic differences in the vasoconstrictor activity of endogenous endothelin-1 in hypertensive patients

Background-The pathogenesis of essential hypertension in blacks may differ from that in whites. In particular, black patients usually present with a salt-sensitive, low-renin form, which in animal models is associated with enhanced activity of endothelin-1 (ET-1). This study aimed to assess whether ethnic differences exist in the vascular activity of ET-1 in normotensive and hypertensive blacks and whites. Methods and Results-Forearm blood flow (FBF) responses to intraarterial infusion of an ETA receptor blocker (BQ-123) were analyzed by plethysmography in 37 normotensive patients and 27 hypertensive patients according to race. BQ-123 did not affect FBF in normotensive subjects (P=0.30), whereas it produced significant vasodilation in hypertensive subjects (P<0.001). In normotensives, FBF response to BQ-123 was similar in white (n = 22) and black (n = 15) patients (P = 0.85). In contrast, in hypertensive patients, the vasodilator effect of ETA receptor blockade was significantly higher in blacks (n = 13) than in whites (n = 14) (P = 0.01). To rule out differences in smooth muscle reactivity, the effects of race on FBF responses to exogenous ET-1 were analyzed in the hypertensive subgroups. Endothelin-1 induced a significant vasoconstriction in both white (n = 7) and black patients (n = 5) (both P<0.001), without differences between them (P = 0.46). In 8 black hypertensives, the response to selective ETA blockade was not modified by nonselective blockade of ET-1 receptors by co-infusion of BQ-123 and BQ-788 (P = 0.66). Conclusions-Hypertensive blacks have enhanced ETA-dependent vasoconstrictor tone, probably related to increased production of ET-1. Given the negative vascular effects of ET-1, this abnormality may contribute to the pathogenesis of hypertension and its complications in black patients.