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(Hypertension. 2004;43:36.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Enhanced Vascular Activity of Endogenous Endothelin-1 in Obese Hypertensive Patients

From the National Heart, Lung, and Blood Institute (C.C., U.C., J.A.P.), Bethesda, Md; Università Cattolica del Sacro Cuore (C.C., M.I.), Rome, Italy; and Washington Hospital Center (U.C., J.A.P.), Washington, DC.

Correspondence to Dr Julio A. Panza, Washington Hospital Center, 110 Irving St NW, Suite 2A 74, Washington, DC 20010. E-mail julio.a.panza{at}medstar.net

Hypertensive patients have increased endothelin-1–dependent vasoconstrictor tone. This abnormality, however, might not be uniformly present in all forms of hypertension, as suggested by experimental studies showing that endothelin-1 activity is enhanced predominantly in low-renin, high-volume models and in insulin-resistant states. Because hypertension in obesity is commonly associated with both expanded plasma volume and insulin resistance, this study sought to determine whether increased body mass index (BMI) in hypertensive patients relates to activation of the endothelin-1 system. Forearm blood flow (FBF) responses (plethysmography) to intra-arterial infusion of an ET_A receptor blocker (BQ-123) were analyzed in hypertensive patients and normotensive control subjects according to BMI. The vasodilator response to BQ-123 was significantly higher in hypertensive patients than in control subjects (P<0.001). During BQ-123, a significant increase in FBF from baseline was observed in obese (BMI 30 kg/m²; P<0.001) and overweight (BMI, 27 to 29.9 kg/m²; P=0.04) but not in lean (BMI <27 kg/m²; P=0.83) hypertensive patients. In contrast, no significant change in FBF was observed during BQ-123 either in obese (P=0.53), overweight (P=0.76), or lean (P=0.93) normotensive subjects. Moreover, a significant correlation between BMI and the vasodilator response to ET_A blockade was observed in hypertensive subjects (R=0.53; P=0.005) but not in control subjects (R=0.11; P=0.58). In human hypertension, increased BMI is associated with enhanced ET_A-dependent vasoconstrictor activity, suggesting that this abnormality may play a role in the pathophysiology of obesity-related hypertension and that targeting the endothelin-1 system may be useful in the treatment of these patients.

Key Words: endothelin • hypertension, obesity • vasculature • atherosclerosis