title: Mental stress induces prolonged endothelial dysfunction via endothelin-A receptors.
abstract: BACKGROUND
  Mental stress is a risk factor for atherosclerosis and may precipitate myocardial ischemia and infarction. Because endothelial dysfunction is an early manifestation of atherosclerosis, we investigated the impact of mental stress on endothelial function. Methods and Results- The effects of a 3-minute mental stress task on endothelium-dependent vasodilation were studied in healthy subjects without cardiovascular risk factors. Flow-mediated (FMD) and nitroglycerin (0.4 mg sublingual)-induced vasodilation were studied before and after mental stress by high-resolution ultrasound of the radial artery. Additionally, FMD was assessed before and 10 to 45 minutes after mental stress during intraarterial infusion of a selective endothelin A receptor antagonist (BQ-123, 1 nmol/min) or saline, respectively. Endothelium-dependent vasodilation was reduced by half for about 45 minutes (8.0+/-1.1% versus 4.1+/-1.0%; P<0.002), whereas endothelium-independent vasodilation to nitroglycerin remained unaffected (15.6+/-1.6 versus 14.3+/-1.3%; NS). Intraarterial infusion of BQ-123, a selective endothelin-A receptor antagonist, but not saline prevented the impairment of endothelium-dependent vasodilation (8.6+/-1.2 versus 9.4+/-1.3%; NS). In contrast, intraarterial infusion of norepinephrine of similar duration as mental stress did not inhibit FMD.
  
  
  CONCLUSIONS
  Mental stress induces prolonged endothelial dysfunction, which is prevented by selective endothelin-A receptor antagonism. This represents a novel and important link between mental stress and atherosclerotic vascular disease.
authors.affiliation: Cardiology, University Hospital, Zürich, Switzerland.
authors.forename: Lukas E
authors.initials: LE
authors.lastname: Spieker
authors.forename: David
authors.initials: D
authors.lastname: Hürlimann
authors.forename: Frank
authors.initials: F
authors.lastname: Ruschitzka
authors.forename: Roberto
authors.initials: R
authors.lastname: Corti
authors.forename: Frank
authors.initials: F
authors.lastname: Enseleit
authors.forename: Sidney
authors.initials: S
authors.lastname: Shaw
authors.forename: Daniel
authors.initials: D
authors.lastname: Hayoz
authors.forename: John E
authors.initials: JE
authors.lastname: Deanfield
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Georg
authors.initials: G
authors.lastname: Noll
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000209:etiology; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D007700:Kinetics; D005996:Nitroglycerin / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D017534:Radial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*; D012307:Risk Factors; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology*; D014463:Ultrasonography; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D014665:Vasodilator Agents; D005996:Nitroglycerin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)