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

Abstract

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. Forearm blood flow (FBF) responses to intraarterial infusion of an ET(A) 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 ET(A) 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 ET(A) blockade was not modified by nonselective blockade of ET-1 receptors by co-infusion of BQ-123 and BQ-788 (P=0.66). Hypertensive blacks have enhanced ET(A)-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.