Phenylephrine contracts rat tail artery by one electromechanical and three pharmacomechanical mechanisms.
There are at least four mechanisms hypothesized to account for excitation-contraction coupling in arterial smooth muscle. 1) Contractile agonists and changes in extracellular [K+] ([K+]o) induce contraction by depolarization, which increases Ca2+ influx; this is the only mechanism involving a change in membrane potential (Em). 2) Contractile agonists release Ca2+ from the intracellular Ca2+ store. 3) Contractile agonists increase Ca2+ influx without changing Em either by activating voltage-dependent L-type Ca2+ channels or by opening other Ca(2+)-permeable channels. 4) Contractile agonists increase intracellular Ca2+ ([Ca2+]i) sensitivity of force; this is the only mechanism that does not involve changes in [Ca2+]i. Each of these mechanisms has been demonstrated in intact, skinned, or dissociated smooth muscle preparations. However, these four mechanisms have not been compared in the same preparation. The goal of this study was to determine which of these four contractile mechanisms are physiologically relevant in the intact rat tail artery. We stimulated deendothelialized rat tail artery with phenylephrine and high [K+]o. We then measured Em with microelectrodes, [Ca2+]i with fura 2, and isometric force with a strain gauge transducer. We find that all four mechanisms contributed to phenylephrine-induced rat tail artery contraction. The majority of phenylephrine-induced contraction was caused by depolarization and by increases in the [Ca2+]i sensitivity of force. Low concentrations of phenylephrine also increased [Ca2+] independent of changes in Em, potentially by increases in Ca2+ influx. Release of Ca2+ from intracellular stores was only observed with high concentrations of phenylephrine. Smooth muscle appears to invoke multiple mechanisms for excitation-contraction coupling.
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
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Chen
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Rembold
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D016257:Fura-2; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail / Q000098:blood supply
D010656:Phenylephrine; D011188:Potassium; D002118:Calcium; D016257:Fura-2; D010646:Phentolamine