Improved endothelium-dependent vasodilation after blockade of endothelin receptors in patients with essential hypertension

• Published in: Circulation (New York, N.Y.) Vol. 105; no. 4; pp. 452 - 456
• Main Authors: CARDILLO, Carmine, CAMPIA, Umberto, KILCOYNE, Crescence M, BRYANT, Melissa B, PANZA, Julio A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 29.01.2002
• Subjects: Acetylcholine - administration & dosage; Acetylcholine - pharmacology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Endothelin Receptor Antagonists; Endothelium, Vascular - physiopathology; Female; Forearm - blood supply; Humans; Hypertension - physiopathology; Infusions, Intra-Arterial; Male; Medical sciences; Middle Aged; Nitroprusside - administration & dosage; Nitroprusside - pharmacology; Oligopeptides - administration & dosage; Oligopeptides - pharmacology; Peptides, Cyclic - administration & dosage; Peptides, Cyclic - pharmacology; Piperidines - administration & dosage; Piperidines - pharmacology; Receptor, Endothelin A; Regional Blood Flow; Vasodilation - drug effects; Vasodilator Agents - administration & dosage; Vasodilator Agents - pharmacology; Human; Hypertension; Regional blood flow; Forearm; Prognosis; Pathogenesis; Cardiovascular disease; Endothelin 1; Vasodilation; Endothelium
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/hc0402.102989

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. Forearm blood flow (FBF) responses to intraarterial infusion of acetylcholine (ACh; 7.5, 15, and 30 microg/min) and sodium nitroprusside (SNP; 0.8,1.6, and 3.2 microg/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). 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.