BACKGROUND: @entity3652 was previously suggested to relax vascular smooth muscle by reducing the intracellular @entity141 concentration ([ @entity141 ]i). However, no direct evidence is available to indicate that @entity3652 reduces the [ @entity141 ]i in vascular smooth muscle of systemic resistance arteries. METHODS: Endothelium-intact or -denuded smooth muscle strips were prepared from @entity35 small mesenteric arteries. Isometric force and [ @entity141 ]i were measured simultaneously in the @entity593 -loaded, endothelium-denuded strips. In some experiments, only isometric force was measured in either the endothelium-intact or beta-escin-treated, endothelium-denuded strips. RESULTS: In the endothelium-intact strips, lower concentrations (< or = 30 microm) of @entity3652 slightly enhanced @entity1063 -induced contraction, whereas higher concentrations (> or = 100 microM) of @entity3652 inhibited both @entity1063 - and @entity4338 -induced contractions. In the @entity593 -loaded strips, @entity3652 (> or = 100 microM) inhibited the increases in both [ @entity141 ]i and force induced by either @entity1063 or @entity4338 . @entity3652 also inhibited the @entity1063 -induced increase in [ @entity141 ]i after treatment with @entity8452 . In the absence of extracellular @entity141 , @entity3652 notably inhibited the @entity1063 -induced increase in [ @entity141 ]i, whereas it only minimally inhibited @entity5834 -induced increase in [ @entity141 ]i. @entity3652 had little influence on the [ @entity141 ]i-force relation during force development to stepwise increment of extracellular @entity141 concentration during either @entity4338 depolarization or @entity1063 stimulation. @entity3652 did not affect @entity141 -activated contractions in the beta-escin membrane-permeabilized strips. CONCLUSIONS: The action of @entity3652 on contractile response to @entity1063 consists of endothelium-dependent vasoconstricting and endothelium-independent vasodilating components. The direct vasorelaxation is largely a result of reduction of[ @entity141 ]i in vascular smooth muscle cells. The [ @entity141 ]i-reducing effects are caused by inhibitions of both voltage-gated @entity141 influx and @entity1063 -induced @entity141 release from the intracellular stores.

Mechanisms of direct inhibitory action of XXXX on vascular smooth muscle in mesenteric resistance arteries.

@entity35 :: ('10116', 'Species') :: ['rat'] @entity8452 :: ('MESH:D012433', 'Chemical') :: ['ryanodine'] @entity5834 :: ('MESH:D002110', 'Chemical') :: ['caffeine'] @entity3652 :: ('MESH:D007649', 'Chemical') :: ['ketamine', 'Ketamine'] @entity593 :: ('MESH:D016257', 'Chemical') :: ['fura-2'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity1063 :: ('MESH:D009638', 'Chemical') :: ['norepinephrine'] @entity4338 :: ('CHEBI:32588', 'Chemical') :: ['KCl']
@entity3652 :: (MESH:D007649,Chemical) :: ['ketamine']
