title: Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension.
abstract: OBJECTIVE
  Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects.
  
  
  METHODS
  In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study 2, young (23 ± 1 years, n = 8), older lifelong sedentary (66 ± 2 years, n = 8) and older lifelong endurance-trained (62 ± 2 years, n = 8) subjects were studied in a cross-sectional design.
  
  
  RESULTS
  Skeletal muscle and plasma endothelin-1 levels were increased with age and plasma endothelin-1 levels were higher in hypertensive than normotensive individuals. Eight weeks of exercise training normalized plasma endothelin-1 levels in the hypertensive subjects and increased the protein expression of the ET(A) receptor in skeletal muscle of normotensive subjects. Similarly, individuals that had performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels.
  
  
  CONCLUSIONS
  Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension. This effect may explain some of the beneficial effects of training on the cardiovascular system in older and hypertensive subjects.
authors.affiliation: Copenhagen Muscle Research Centre, University of Copenhagen, Copenhagen, Denmark. mnyberg@ifi.ku.dk
authors.forename: M
authors.initials: M
authors.lastname: Nyberg
authors.forename: S P
authors.initials: SP
authors.lastname: Mortensen
authors.forename: Y
authors.initials: Y
authors.lastname: Hellsten
mesh_terms: D000367:Age Factors; D000368:Aged; D000375:Aging / Q000097:blood*; D000704:Analysis of Variance; D003430:Cross-Sectional Studies; D019332:Endothelin-1 / Q000097:blood*; D015444:Exercise; D005080:Exercise Test; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D057185:Sedentary Behavior; D013997:Time Factors; D055815:Young Adult
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B