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Aim To evaluate the vasorelaxant effect of two new chemical entities, J35242 and J35243, on iso-lated rat thoracic aorta rings as Rho-kinase inhibitors, and further to explore the underlying mechanisms of these two compounds. Methods Isolated rat thoracic aorta rings pre-contracted by KCl or norepinephrine ( NE) were used to evaluate the vasodilatory effect of J35242 and J35243 . Through the interventions of sev-eral tool drugs, the mechanisms of compounds concern-ing endothelium, K+ channels and Ca2+ were studied. Results J35242 and J35243 showed potent relaxant effect on both KCl and NE pre-contracted vessels, and exhibited partial endothelium dependency. L-NAME and Methylene Blue( MB) could influence the relaxant effect of these compounds. Meanwhile, the compounds could inhibit intracellular Ca2+ release and extracellu-lar Ca2+ influx, which indicated that the compounds might block the calcium channels to relax the vessels. In addition, the two compounds probably did not dilate the aorta rings through opening potassium channels. Conclusions J35242 and J35243 have vasorelaxant effects on vessels in vitro and the potency of J35242 is stronger than that of J35243 . The underlying mecha-nisms might be endothelium-dependent. Also the com-pounds might block Ca2+ channels, lowering intracel-lular Ca2+ concentration to relax the vessels.
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Objective To observe the vasodilation effect of extract of Jasminum samba (EJs), a kind of traditional Chinese medicine, on ex vivo rat thoracic aortic rings, and to investigate its mechanism. Methods On ex vivo aortic ring perfusion device, influence of EJs on contraction of the aorta induced by phenylephrine (PE) or potassium chloride (KCl) was observed. Influence of N-nitro-L-arginine-methylester ( L-NAME ), barium chloride ( BaCl2 ), glibenclamide ( Gli ) on vasodilating effect of EJs (0. 5, 1, 2, 4, 8 g·L-1 ) was detected. Effect of EJs on the contraction of calcium chloride (CaCl2 ) and PE in Ca2+-free medium was detected. [ Ca2+ ] i in vascular smooth muscle cells was determined by using laser scanning confocal microscope (LSCM). Results In blood vessels with intact endothelium, EJs concentration-dependently decreased PE- or KCl-induced vasoconstriction, the maximum dilating effect being (105. 0±3. 2)% and (78. 0±6. 5)% , respectively; L-NAME affected the vasodilatory effect of EJs on thoracic aorta rings ( P<0. 01), the maximum dilatory effect being (58. 0 ± 6. 9)% . BaCl2 and Gli had significant influence on vasodilation of EJs, and the contraction was obviously attenuated (P<0. 01), the maximum dilatory effect being (37. 0±5. 2)% and (78. 0±10. 0)% , respectively. EJs significantly inhibited contracting effect of PE on thoracic aorta rings in Ca2+-free medium (P<0. 01). The maximum contraction effect was (70. 0±6. 3)% . EJs inhibited CaCl2-induced vasoconstriction (0. 5-8 mmol·L-1 ), and vasoconstriction was decreased by (65. 0±3. 2)% . LSCM recorded that Fmax / F0 of 4 and 8 g·L-1 EJs was (2. 0±0. 2) and (1. 5±0. 2), respectively. Conclusion EJs exerted a dose-dependent vasodilating effect on rat isolated aorta rings. The mechanism might be related to promoting NO release, activating K+channels and decreasing the concentration of cytoplasmic Ca2+.
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Objective To investigate the effects of total alkaloids in Buxus microphylla leaves (ABML) on isolated rats thoracic aorta rings,and then to explore the possible mechanisms underlying the effects.MethodsThoracic aortas of Wistar rats were isolated,removed,and mounted onto an organ bath.The effects of ABML at different concentration on the contraction of isolated thoracic aorta rings (with and without endothelium) precontracted with KC1 or PE were observed with organ bath technique.Dose-effect curves of CaCl2 were recorded by organ bath technique.The concentration of intracellular Ca2+ ([Ca2+]i) increased by PE,KCI,and caffeine in the presence of ABML was determined using Ca2+ sensitive fluorescence indicator Fura-2/AM loaded thoracic aorta vascular smooth muscle (VSM) cells of rats.ResultsIn aorta rings precontracted with PE and KCI,ABML produced concentrationdependent relaxation in both intact and denuded endothelium ring groups.There was no difference in the inhibition of contraction between the intact and denuded endothelium ring groups at the same concentration.Exposure of isolated thoracic aorta rings to ABML led to a significant reduction in the contracting response induced by CaCI2,and shifted the cumulative concentration-response curves to right.ABML could significantly inhibit the extracellular Ca2+ influx induced by PE and KCI under [Ca2+]0 of 1.5 mmol/L,with inhibitory ratios of 40.2％ and 49.9％,respectively.In the case of Ca2+-free,ABML could significantly inhibit the intracellular Ca2+ release induced by PE,with inhibitory ratio of 72.4％.ConclusionABML relaxes thoracic aorta VSM cells by suppressing influx of extracellular Ca2+ via voltage-dependent Ca2+ channel and receptor-operated Ca2+ channel.
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Objective To observe effect of large blood vessel hypoxia on the Wister rat′s NO activity. Methods Thoracic aorta rings model with full endothelium and removed endothelium of Wistar rat were prepared , hypoxia stimulated aorta rings and noted changes of constriction extent. Results Endothelium full , removed endothelium aorta rings by hypoxia contract extent difference was 598?42mg and 208?38mg, both had significance discrepancy (P0.05), and NTG made blood vessel contract to reduce range, reach 57.21% (P
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The establishment of a modified method to evaluate angiogenesis of rat rings in serum-free medium was investigated in this paper. The aorta rings of Wistar rats were embedded in fibrinogen gel in 48 well plates, and cultured in an optimized serum free medium MCDB131. Results indicated that new capillaries spouted on 4th day, and entered into growth phase from 6th day, and peaked on 13th day and remained unchanged thereafter.
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The inhibitory effects of cicletanine (Cic) and bepridil (Bep) on norepinephrine (NE)-and KCl-induced contractions were studied in isolated thoracic aorta rings of male Sprague-Dowley rats. It was found that Cic had a more potent effect on NE-induced contraction than on KCHnduced contraction. In. contrast, Bep had a more potent action on KCHnduced contraction. When the aorta rings were incubated with Cic and Bep, a potentialized inhibitory effect was observed on KCh but not NE-induced contractions. These effects were independent of the presence of endothelium. The results suggest that Cic and Bep have different action sites and properties on vascular smooth muscles.