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

2002; Lippincott Williams & Wilkins; Volume: 105; Issue: 4 Linguagem: Inglês

10.1161/hc0402.102989

1524-4539

Carmine Cardillo, Umberto Campia, Crescence M. Kilcoyne, Melissa B. Bryant, Julio A. Panza,

Blood Pressure and Hypertension Studies

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.