title: Effects of β₂-agonists on force during and following anoxia in rat extensor digitorum longus muscle.
abstract: Electrical stimulation of isolated muscles may lead to membrane depolarization, gain of Na(+), loss of K(+) and fatigue. These effects can be counteracted with β(2)-agonists possibly via activation of the Na(+)-K(+) pumps. Anoxia induces loss of force; however, it is not known whether β(2)-agonists affect force and ion homeostasis in anoxic muscles. In the present study isolated rat extensor digitorum longus (EDL) muscles exposed to anoxia showed a considerable loss of force, which was markedly reduced by the β(2)-agonists salbutamol (10(-6) M) and terbutaline (10(-6) M). Intermittent stimulation (15-30 min) clearly increased loss of force during anoxia and reduced force recovery during reoxygenation. The β(2)-agonists salbutamol (10(-7)-10(-5) M) and salmeterol (10(-6) M) improved force development during anoxia (25%) and force recovery during reoxygenation (55-262%). The effects of salbutamol on force recovery were prevented by blocking the Na(+)-K(+) pumps with ouabain or by blocking glycolysis with 2-deoxyglucose. Dibutyryl cAMP (1 mM) or theophylline (1 mM) also improved force recovery remarkably. In anoxic muscles, salbutamol decreased intracellular Na(+) and increased (86)Rb uptake and K(+) content, indicating stimulation of the Na(+)-K(+) pumps. In fatigued muscles salbutamol induced recovery of excitability. Thus β(2)-agonists reduce the anoxia-induced loss of force, leading to partial force recovery. These data strongly suggest that this effect is mediated by cAMP stimulation of the Na(+)-K(+) pumps and that it is not related to recovery of energy status (PCr, ATP, lactate).
authors.affiliation: Department of Biomedicine, Aarhus University, Denmark. af@fi.au.dk
authors.forename: A
authors.initials: A
authors.lastname: Fredsted
authors.forename: H
authors.initials: H
authors.lastname: Gissel
authors.forename: N
authors.initials: N
authors.lastname: Ortenblad
authors.forename: T
authors.initials: T
authors.lastname: Clausen
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018763:Muscle Fatigue / Q000187:drug effects* / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000068299:Salmeterol Xinafoate; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013726:Terbutaline / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D010042:Ouabain; D003994:Bucladesine; D000068299:Salmeterol Xinafoate; D003847:Deoxyglucose; D012964:Sodium; D013806:Theophylline; D000254:Sodium-Potassium-Exchanging ATPase; D013726:Terbutaline; D000420:Albuterol; D011188:Potassium