Interaction of @entity9409 ( XXXX ) with @entity1808 on @entity460 mobilization in vascular smooth muscle cells.

@entity101 @entity141 @entity26 @entity1855 @entity1808 @entity9409 @entity593 @entity460 @entity35 @entity551
@entity9409 ( @entity9409 ) was shown to lower blood pressure in @entity35 models of @entity101 . Thus, there is evidence that-besides its chelating properties- @entity9409 has a direct vascular effect, e.g. through scavenging of reactive @entity26 species (ROS). We speculated that, in addition, intracellular @entity460 mobilization may be involved in this action. Therefore, the present study examined the effects of @entity9409 on @entity141 mobilization in cultured vascular smooth muscle cells (VSMCs) from @entity35 aorta. Intracellular free @entity141 concentration ([ @entity141 ](i)) was measured with @entity593 AM. In a first series of experiments @entity9409 , 10(-11) to 10(-6)M, induced an immediate dose-dependent up to 4-fold rise of [ @entity141 ](i) (P<0.001) which was almost completely blunted by the @entity460 channel blocker @entity1855 or the intracellular @entity460 release blocker TMB-8. In a second series of experiments, when VSMCs were exposed acutely to @entity9409 (10(-11) to 10(-6)M), the @entity1808 (10(-8)M)-induced rise in [ @entity141 ](i) to 295+/-40nM was attenuated at the average by 49% independent of the dose of @entity9409 . Preincubation of VSMCs with @entity9409 (10(-6)M) for 60min reduced basal [ @entity141 ](i) by 77% (P<0.001) and dose-dependently attenuated the @entity1808 (10(-8)M)-induced rise in [ @entity141 ](i) between 28 and 69% at concentrations between 10(-9) and 10(-5)M @entity9409 , respectively (P<0.05 and <0.01). In the presence of TMB-8, which attenuated the @entity1808 (10(-8)M)-induced rise in [ @entity141 ](i) by 66%, @entity9409 (10(-6)M) had no additional suppressive effect on [ @entity141 ](i). The results suggest that @entity9409 acutely raises [ @entity141 ](i) by stimulating transmembrane @entity460 influx via L-type @entity460 channels and by @entity460 release from intracellular stores followed by a decrease in [ @entity141 ](i) probably due to cellular @entity460 depletion. Thus, in addition to its action as scavenger of ROS, which in part mediate the vasoconstrictor response, e.g. to @entity1808 , @entity9409 may exert its @entity551 effect through decreasing total cell @entity460 , thereby attenuating the vasoconstrictor-induced rise in [ @entity141 ](i) in VSMCs.
