title: Effects of ageing and regular aerobic exercise on endothelial fibrinolytic capacity in humans.
abstract: The capacity of the vascular endothelium locally to release tissue-type plasminogen activator (t-PA) is critical for effective endogenous fibrinolysis. We determined the influence of ageing and regular aerobic exercise on the net release of t-PA across the human forearm in vivo using both cross-sectional and intervention approaches. First, we studied 62 healthy men aged 22-35 or 50-75 years of age who were either sedentary or endurance exercise-trained. Net endothelial release rates of t-PA were calculated as the product of the arteriovenous concentration gradient and forearm plasma flow to intra-arterial bradykinin and sodium nitroprusside. Second, we studied 10 older (60 +/- 2 years) healthy sedentary men before and after a 3 month aerobic exercise intervention. Net endothelial t-PA release was significantly blunted with age in the sedentary men. At the highest dose of bradykinin the increase in t-PA antigen release was approximately 35 % less (P < 0.05) in the older (from -1.0 +/- 0.4 to 37.8 +/- 3.8 ng (100 ml tissue)(-1) min(-1)) compared with young (from 0.1 +/- 0.6 to 56.6 +/- 9.2 ng (100 ml tissue)(-1) min(-1)) men. In contrast, the endurance-trained men did not demonstrate an age-related decline in the net release of t-PA antigen. After the exercise intervention, the capacity of the endothelium to release t-PA increased approximately 55 % (P < 0.05) to levels similar to those of the young adults and older endurance-trained men. Regulated endothelial t-PA release declines with age in sedentary men. Regular aerobic exercise may not only prevent, but could also reverse the age-related loss in endothelial fibrinolytic function.
authors.affiliation: Integrative Vascular Biology Laboratory, Department of Kinesiology and Applied Physiology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Derek T
authors.initials: DT
authors.lastname: Smith
authors.forename: Greta L
authors.initials: GL
authors.lastname: Hoetzer
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Greiner
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
authors.forename: Christopher A
authors.initials: CA
authors.lastname: DeSouza
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001920:Bradykinin / Q000008:administration & dosage; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology*; D015444:Exercise / Q000502:physiology*; D005342:Fibrinolysis; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000378:metabolism; D010806:Physical Education and Training; D010807:Physical Endurance; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D018727:Muscarinic Antagonists; D010959:Tissue Plasminogen Activator; D001920:Bradykinin