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(Circulation. 2002;105:452.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Improved Endothelium-Dependent Vasodilation After Blockade of Endothelin Receptors in Patients With Essential Hypertension

Carmine Cardillo, MD; Umberto Campia, MD; Crescence M. Kilcoyne, RN, MS; Melissa B. Bryant, RN; Julio A. Panza, MD

From the Cardiology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Md. Dr Cardillo is currently at Università Cattolica del Sacro Cuore, Rome, Italy.

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

Background— Hypertensive patients have both impaired endothelium-dependent vasodilation and increased activity of the endothelin (ET-1) system, which participate in their increased vascular tone and may predispose them to atherosclerosis. This study investigated the contribution of increased ET-1 activity to the impaired endothelium-dependent vasodilator function of hypertensive patients.

Methods and Results— Forearm blood flow (FBF) responses to intraarterial infusion of acetylcholine (ACh; 7.5, 15, and 30 µg/min) and sodium nitroprusside (SNP; 0.8,1.6, and 3.2 µg/min) were assessed by strain-gauge plethysmography before and after nonselective blockade of ET_A and ET_B receptors by combined infusion of BQ-123 (ET_A blocker; 100 nmol/min) and BQ-788 (ET_B blocker; 50 nmol/min). During saline administration, the vasodilator response to ACh was significantly blunted in hypertensive patients compared with controls (P<0.001), whereas the vasodilator effect of SNP was not different between groups (P=0.74). Blockade of ET-1 receptors resulted in a significant increase in FBF from baseline in hypertensive patients (P<0.008) but not in controls (P=0.15). In hypertensive patients, a combined ET_A/B blockade resulted in a significant potentiation of the vasodilator response to ACh compared with saline (P=0.01), whereas the response to SNP was unchanged (P=0.44). In contrast, the response to ACh was not significantly modified by ET-1 receptor antagonism in healthy subjects (P=0.14 compared with saline).

Conclusions— These findings indicate that blockade of ET-1 receptors improves endothelium-dependent vasodilator function in hypertensive patients, thereby suggesting that an increased ET-1 activity may play a role in the pathophysiology of this abnormality.

Key Words: endothelin • endothelium • vasodilation • hypertension

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