No abstract

SUMMARY1. Effects of noradrenaline (NAd) on changes in cellular Ca2+ concentration ([Ca21]i) and tension were investigated, and these effects were compared with those evoked by 128 mm K+ or caffeine in intact smooth muscle strips or by inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) or caffeine in ,-escin-treated chemically skinned smooth muscle strips of the rabbit mesenteric artery.2. In physiological solution containing 2-6 mm Ca2+, application of 128 mm K+ or 10 1UM NAd produced a phasic, followed by a tonic increase in [Ca2+]

The present results indicate that in vivo blockade of 5-HT(2A) receptors leads to an inhibition of intimal hyperplasia in rabbit vein graft. It is suggested that an increased function of endothelium-derived NO through a reduction in endothelial superoxide production may be a possible underlying mechanism for this. These novel findings support the clinical usefulness of sarpogrelate for preventing intimal hyperplasia in vein graft after bypass grafting.

1 Effects of (-)-cromakalim (lemakalim) on tension and Ca2+ mobilization induced by noradrenaline (NA) were investigated by measuring intracellular Ca2" concentration ([Ca2"]), isometric tension and production of inositol-1,4,5-trisphosphate (IP3) in smooth muscle strips of the rabbit mesenteric artery.2 In thin smooth muscle strips, 1OpUM NA produced a large phasic, followed by a small tonic increase in [Ca2'ji, which correlated well with the evoked phasic and tonic contractions, respectively. Lemakalim (0. 4 In fl-escin-skinned strips, 1OMm NA increased [Ca2+]i in Ca2+-free solution containing 50pM EGTA, 3 pM guanosine triphosphate (GTP) and 2,pM Fura 2 after the storage sites were loaded by application of 0.3/iM Ca2+ for 2 min, suggesting that Ca2+ is released from intracellular storage sites following activation of the a-adrenoceptor. Lemakalim (1 pM) did not inhibit the Ca2+ release from storage sites induced by NA. 5 We conclude that lemakalim inhibits NA-induced Ca2 + release due to inhibition of NA-induced 'P3 production in a manner dependent on the membrane potential and causes inhibition of the phasic contraction induced by NA.

1 This study was undertaken to determine whether long-term in vivo administration of nitroglycerine (NTG) downregulates the hyperpolarization induced by acetylcholine (ACh) in aortic valve endothelial cells (AVECs) of the rabbit and, if so, whether antioxidant agents can normalize this downregulated hyperpolarization. 2 ACh (0.03-3 mM) induced a hyperpolarization through activations of both apamin-and charybdotoxin-sensitive Ca 2 þ -activated K þ channels (K Ca ) in rabbit AVECs. The intermediateconductance K Ca channel (IK Ca ) activator 1-ethyl-2-benzimidazolinone (1-EBIO, 0.3 mM) induced a hyperpolarization of the same magnitude as ACh (3 mM).3 The ACh-induced hyperpolarization was significantly weaker, although the ACh-induced [Ca 2 þ ] i increase was unchanged, in NTG-treated rabbits (versus NTG-untreated control rabbits). The hyperpolarization induced by 1-EBIO was also weaker in NTG-treated rabbits. 4 The reduced ACh-induced hyperpolarization seen in NTG-treated rabbits was not modified by in vitro application of the superoxide scavengers Mn-TBAP, tiron or ascorbate, but it was normalized when ascorbate was coadministered with NTG in vivo. 5 Superoxide production within the endothelial cell (estimated by ethidium fluorescence) was increased in NTG-treated rabbits and this increased production was normalized by in vivo coadministration of ascorbate with the NTG. 6 It is suggested that long-term in vivo administration of NTG downregulates the ACh-induced hyperpolarization in rabbit AVECs, possibly through chronic actions mediated by superoxide.