title: Exercise training enhances flow-induced vasodilation in skeletal muscle resistance arteries of aged rats: role of PGI2 and nitric oxide.
abstract: Flow-induced vasodilation is attenuated with old age in rat skeletal muscle arterioles. The purpose of this study was to determine whether diminished cyclooxygenase (COX) signaling contributes to the age-induced attenuation of flow-induced vasodilation in gastrocnemius muscle arterioles and to determine whether, and through which mechanism(s), exercise training restores this deficit in old rats. Fischer 344 rats (3 and 22 mo old) were assigned to a sedentary or exercise-trained group. First-order arterioles were isolated from the gastrocnemius muscles, cannulated, and pressurized to 70 cm H(2)O. Diameter changes were determined in response to graded increases in intraluminal flow in the presence and absence of nitric oxide synthase (NOS) inhibition [10(-5) M N(G)-nitro-L-arginine methyl ester (L-NAME)], COX inhibition (10(-5) M indomethacin), or combination NOS (10(-5) M L-NAME) plus COX (10(-5) M indomethacin) inhibition. Aging reduced flow-induced vasodilation in gastrocnemius muscle arterioles. Exercise training restored responsiveness to flow in arterioles of aged rats and enhanced flow-induced vasodilation in arterioles from young rats. L-NAME inhibition of flow-induced vasodilation was greater in arterioles from old rats compared with those from young rats and was increased after exercise training in arterioles from both young and old rats. Although the indomethacin-sensitive portion of flow-induced dilation was not altered by age or training, both COX-1 mRNA expression and PGI(2) production increased with training in arterioles from old rats. These data demonstrate that exercise training restores flow-induced vasodilation in gastrocnemius muscle arterioles from old rats and enhances flow-induced vasodilation in gastrocnemius muscle arterioles from young rats. In arterioles from both old and young rats, the exercise training-induced enhancement of flow-induced dilation occurs primarily through a NOS mechanism.
authors.affiliation: Department of Health and Kinesiology, University of Texas at Tyler, Tyler, TX, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Spier
authors.forename: Michael D
authors.initials: MD
authors.lastname: Delp
authors.forename: John N
authors.initials: JN
authors.lastname: Stallone
authors.forename: James M
authors.initials: JM
authors.lastname: Dominguez
authors.forename: Judy M
authors.initials: JM
authors.lastname: Muller-Delp
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001783:Blood Flow Velocity; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D005082:Physical Exertion / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012039:Regional Blood Flow; D015398:Signal Transduction; D015854:Up-Regulation; D014655:Vascular Resistance; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin