title: Variation in genes in the endothelin pathway and endothelium-dependent and endothelium-independent vasodilation in an elderly population.
abstract: OBJECTIVE
  Indirect evidences by blockade of the endothelin receptors have suggested a role of endothelin in endothelium-dependent vasodilation. This study aimed to investigate whether circulating levels of endotehlin-1 or genetic variations in genes in the endothelin pathway were related to endothelium-dependent vasodilation.
  
  
  METHODS
  In 1016 seventy-year-old participants of the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (52% women), we measured endothelium-dependent vasodilation using the invasive forearm technique with acetylcholine given in the brachial artery (EDV) and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD). Plasma endothelin-1 levels were measured and 60 SNPs in genes in the endothelin pathway (ECE1, EDN1, EDNRA, EDNRB) were genotyped.
  
  
  RESULTS
  No significant associations were found between circulating endothelin levels and EDV or FMD. No single genotype was related to EDV or FMD following adjustment for multiple testing, but a genotype score for 3 SNPs (rs11618266 in EDNRB, rs17675063 in EDNRA, rs3026868 in ECE1) was significantly related to EDV (beta coefficient 0.070, 95% CI 0.025-0.12, P = 0.002) when adjusting for gender, systolic blood pressure, HDL and LDL cholesterol, serum triglycerides, BMI, diabetes, smoking, antihypertensive medication or statins and CRP. This score was also related to nitroprusside-induced vasodilation in the forearm.
  
  
  CONCLUSIONS
  A combination of genotypes in the endothelin pathway was related to both endothelium-dependent and endothelium-independent vasodilation in forearm resistance vessels, but not in the brachial artery in an elderly population, giving evidence for a role of the endothelin system in resistance vessel reactivity independent of major cardiovascular risk factors.
authors: Department of Medical Sciences, Uppsala University, Stockholm, Sweden. lars.lind@medsci.uu.se
authors: L
authors: L
authors: Lind
authors: A-C
authors: AC
authors: Syvänen
authors: T
authors: T
authors: Axelsson
authors: P
authors: P
authors: Lundmark
authors: S
authors: S
authors: Hägg
authors: A
authors: A
authors: Larsson
mesh_terms: D000367:Age Factors; D000368:Aged; D000375:Aging / Q000097:blood / Q000235:genetics*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D019332:Endothelin-1 / Q000097:blood* / Q000235:genetics*; D000072396:Endothelin-Converting Enzymes; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005542:Forearm / Q000098:blood supply*; D005838:Genotype; D006801:Humans; D007261:Infusions, Intra-Arterial; D016014:Linear Models; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D044022:Receptor, Endothelin A / Q000235:genetics; D044023:Receptor, Endothelin B / Q000235:genetics; D012039:Regional Blood Flow; D013548:Sweden; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects / Q000235:genetics*; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014665:Vasodilator Agents; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes