title: Integrated Ca(2+) signaling between smooth muscle and endothelium of resistance vessels.
abstract: Cell-cell communication in the arteriolar wall was examined using the Ca(2+)-sensitive indicator fura-2 and the Ca(2+) buffer BAPTA as means of measuring and buffering cellular Ca(2+). The experiments focused on the role of endothelial cell [Ca(2+)](i) in modulating phenylephrine (PE)-induced contractions in in vitro arterioles of the hamster cremaster. Fura-2-AM and BAPTA-AM were applied intraluminally to accomplish endothelium-specific loading. PE was applied to short segments of arterioles using pressure-pulse ejection from a micropipette. Under control conditions at the site of stimulation, PE elicited a strong vasoconstriction preceded by an increase in endothelial cell [Ca(2+)](i). A very small biphasic conducted response was observed at sites upstream from the stimulation site. BAPTA sharply reduced the measured Ca(2+) response in the endothelium. This was associated with an enhanced local contractile response. In addition, the biphasic conducted response was converted into a strong conducted vasoconstriction. PE caused an initial rise in smooth muscle [Ca(2+)](i) at the stimulated site, which was followed by a rapid decrease below baseline. Endothelial cell loading of BAPTA had minimal effect on the initial [Ca(2+)](i) peak but eliminated the secondary decrease in smooth muscle [Ca(2+)](i). Intraluminal application of charybdotoxin plus apamin mimicked the change in vasomotor state induced by BAPTA. These data lead us to hypothesize that, after smooth muscle stimulation, intercellular Ca(2+) signaling between smooth muscle and endothelium causes a secondary rise in endothelial cell Ca(2+), which triggers a hyperpolarizing event and initiates a conducted vasodilation. We conclude that smooth muscle and endothelium operate as a functional unit in these vessels.
authors.affiliation: First Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yashiro
authors.forename: B R
authors.initials: BR
authors.lastname: Duling
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D006224:Cricetinae; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005456:Fluorescent Dyes; D016257:Fura-2; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D018482:Muscle, Skeletal / Q000098:blood supply; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D014655:Vascular Resistance; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D005456:Fluorescent Dyes; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D010656:Phenylephrine; D004533:Egtazic Acid; D002118:Calcium; D016257:Fura-2