title: Improved endothelium-dependent vasodilation after blockade of endothelin receptors in patients with essential hypertension.
abstract: 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.
  
  
  RESULTS
  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).
  
  
  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.
authors.affiliation: Cardiology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Carmine
authors.initials: C
authors.lastname: Cardillo
authors.forename: Umberto
authors.initials: U
authors.lastname: Campia
authors.forename: Crescence M
authors.initials: CM
authors.lastname: Kilcoyne
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Bryant
authors.forename: Julio A
authors.initials: JA
authors.lastname: Panza
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D044022:Receptor, Endothelin A; D012039:Regional Blood Flow; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D014665:Vasodilator Agents; D009599:Nitroprusside; C086539:BQ 788; D000109:Acetylcholine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)