title: Ageing reduces nitric-oxide- and prostaglandin-mediated vasodilatation in exercising humans.
abstract: In older humans, infusions of endothelial agonists suggest endothelial dysfunction, due in part to less nitric oxide (NO)- and prostaglandin (PG)-mediated vasodilatation, and a shift toward PG-mediated vasoconstriction. Ageing can also be associated with lower exercise blood flow (exercise hyperaemia), but the vascular mechanisms mediating this remain unknown. Notably, in young adults, inhibition of NO and PGs during exercise decreases exercise hyperaemia by approximately 20 and approximately 12%, respectively. We tested our first hypothesis that in older humans inhibition of NO would decrease hyperaemia, but that inhibition of PGs would increase hyperaemia by blocking vasoconstrictor PGs. Fifteen older subjects (65 +/- 3 years) performed dynamic forearm exercise for 20 min (20 contractions min(-1)). Forearm blood flow (FBF) was measured beat-to-beat with Doppler ultrasound, while saline or drugs were infused sequentially via brachial artery catheter in the exercising forearm. After achieving steady-state exercise, L-NAME (25 mg) was infused over 5 min to inhibit NO synthase. After a further 2 min of exercise (saline), ketorolac (6 mg) was infused over 5 min to inhibit PGs, followed by a further 3 min of exercise with saline. Drug order was reversed in seven subjects. L-NAME reduced steady-state exercise hyperaemia by 12 +/- 3% in older subjects (P<0.01), whereas ketorolac had no net effect on blood flow (3 +/- 6%, P>0.4). The effects of l-NAME and ketorolac were independent of drug order. By comparing these results with our previous results in young adults, we tested our second hypothesis that in older humans inhibition of NO or PGs would have less impact on exercise hyperaemia due to less vasodilatation from these signals. Our results suggest that, compared with young adults, in older humans the relative contribution of NO to exercise hyperaemia is reduced approximately 45% (22 +/- 4 versus 12 +/- 3%), but the role of PG in mediating vasodilatation is lost in ageing human skeletal muscle. Lower exercise hyperaemia in older humans may be mediated in part by less NO- and PG-mediated vasodilatation during exercise.
authors.affiliation: Department of Kinesiology, 1149A Natatorium, University of Wisconsin, Madison, WI 53706, USA. wschrage@education.wisc.edu
authors.forename: William G
authors.initials: WG
authors.lastname: Schrage
authors.forename: John H
authors.initials: JH
authors.lastname: Eisenach
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Joyner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D020910:Ketorolac / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005082:Physical Exertion / Q000502:physiology*; D011453:Prostaglandins / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D020910:Ketorolac