title: Eicosapentaenoic acid inhibits vasopressin-activated Ca2+ influx and cell proliferation in rat aortic smooth muscle cell lines.
abstract: The purpose of this study was to clarify how eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, modulates the vascular action of vasopressin in rat aortic smooth muscle cell lines. The effects of EPA on Ca2+ mobilization and DNA synthesis elicited by vasopressin were investigated and compared to those of Ca2+ channel blocking agents, by means of Ca2+ measurements and the incorporation of [3H]thymidine. Patch-clamp techniques were also employed. Vasopressin (100 nM) elicited an initial peak of intracellular Ca2+ ([Ca2+]i), followed by a sustained phase due to Ca2+ entry. Nifedipine or nicardipine (1 microM), a potent L-type Ca2+ channel blocker, partly inhibited the sustained phase, but La3+ completely abolished it. EPA (10 microM) also inhibited it even in the presence of nicardipine. Under voltage-clamp conditions with CsCl-internal solution, depolarizing pulses positive to -30 mV from a holding potential of -40 mV elicited a slow inward current. The inward current was blocked by La3+, nicardipine, and nifedipine (1 microM), suggesting that the inward current mainly consisted of the voltage-dependent L-type Ca2+ channel (ICa.L). EPA (1-30 microM) also inhibited ICa.L in a concentration-dependent manner. The inhibitory effect of EPA was observed at concentrations higher than 1 microM, and its half-maximal inhibitory concentration (IC50) was 7.6 microM. Vasopressin induced a long-lasting inward current at a holding potential of -40 mV. The vasopressin-induced current was considered as a non-selective cation current (Icat) with a reversal potential of approximately +0 mV. Both nifedipine and nicardipine (10 microM) failed to inhibit it significantly, but La3+ completely abolished Icat. EPA also inhibited vasopressin-induced Icat in a concentration-dependent manner; its IC50 value was 5.9 microM. Vasopressin (100 nM) stimulated [3H]thymidine incorporation. Exclusion of extracellular Ca2+ with EGTA or La3+ markedly inhibited it. EPA (3-30 microM) also inhibited the incorporation induced by vasopressin, while nifedipine and nicardipine (1 microM) only partly inhibited it. These results suggested that EPA, unlike nifedipine and nicardipine, inhibited vasopressin-induced Ca2+-entry and proliferation in rat vascular smooth muscle cells, where the inhibitory effects of EPA on Icat as well as ICa.L might be involved. Thus, EPA would exert hypotensive and antiatherosclerotic effects.
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Asano
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Iwasawa
authors.forename: Y
authors.initials: Y
authors.lastname: Asakura
authors.forename: T
authors.initials: T
authors.lastname: Morita
authors.forename: F
authors.initials: F
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Tomaru
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Goto
authors.forename: T
authors.initials: T
authors.lastname: Toyo-oka
authors.forename: M
authors.initials: M
authors.lastname: Soma
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Okuda
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D016623:Ion Pumps / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D016623:Ion Pumps; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D015118:Eicosapentaenoic Acid; D009529:Nicardipine; D009543:Nifedipine; D002118:Calcium