title: Resting load regulates vascular sensitivity by a cytosolic Ca(2+)-insensitive mechanism.
abstract: The cellular mechanism underlying the regulation of the contraction of vascular smooth muscles by resting load is unknown. To determine the effects of changes in the resting load on vascular sensitivity to high K+ and to 9,11-dideoxy-11 alpha, 9 alpha-epoxy-methanoprostaglandin F2 alpha (U-46619), the force and cytosolic calcium concentration ([Ca2+]i) of arterial strips were recorded at resting loads of 200 (optimal load), 50, and 10 mg. A decrease in the resting load elicited a small decrease in the basal [Ca2+]i level without affecting the extent of maximal [Ca2+]i elevation induced by either stimulus. Through a decrease in the resting load, the concentration-response curves for the force development of high K+ or of U-46619 shifted to the right, whereas those for [Ca2+]i did not. We conclude that the basal [Ca2+]i level and the force development, but not the agonist-induced [Ca2+]i signals, of vascular smooth muscles depend on the resting load. We response that the resting load regulates the sensitivity of vascular smooth muscles, irrespective of types of stimuli, through a [Ca2+]i-insensitive mechanism.
authors.affiliation: Division of Molecular Cardiology, Research Institute of Angiocardiology, Kyushu University, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyagi
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: J
authors.initials: J
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Fukui
authors.forename: H
authors.initials: H
authors.lastname: Kanaide
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D016257:Fura-2; D066298:In Vitro Techniques; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009121:Muscle Denervation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011188:Potassium; D002118:Calcium; D016257:Fura-2