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Brazilin isolated from the heartwood of Caesalpinia sappan L induces endothelium-dependent and -independent relaxation of rat aortic rings.

Yan Y, Chen YC, Lin YH, Guo J, Niu ZR, Li L, Wang SB, Fang LH, Du GH - Acta Pharmacol. Sin. (2015)

Bottom Line: The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin.Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC.Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca(2+) channels.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing 100050, China.

ABSTRACT

Aim: Brazilin is one of the major constituents of Caesalpinia sappan L with various biological activities. This study sought to investigate the vasorelaxant effect of brazilin on isolated rat thoracic aorta and explore the underlying mechanisms.

Methods: Endothelium-intact and -denuded aortic rings were prepared from rats. The tension of the preparations was recorded isometrically with a force displacement transducer connected to a polygraph. The phosphorylation levels of ERK1/2 and myosin light chain (MLC) were analyzed using Western blotting assay.

Results: Application of brazilin (10-100 μmol/L) dose-dependently relaxed the NE- or high K(+)-induced sustained contraction of endothelium-intact aortic rings (the EC50 was 83.51±5.6 and 79.79±4.57 μmol/L, respectively). The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin. In addition, pre-incubation with brazilin dose-dependently attenuated the vasoconstriction induced by KCl, NE or Ang II. Pre-incubation with brazilin also markedly suppressed the high K(+)-induced extracellular Ca(2+) influx and NE-induced intracellular Ca(2+) release in endothelium-denuded aortic rings. Pre-incubation with brazilin dose-dependently inhibited the NE-stimulated phosphorylation of ERK1/2 and MLC in both endothelium-intact and -denuded aortic rings.

Conclusion: Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC. Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca(2+) channels.

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Inhibitory effects of brazilin (25, 50, and 100 μmol/L) on concentration-response curves of NE (10−9–10−6 mol/L) (A and B) and KCl (10–60 mmol/L) (C and D) in endothelium-intact aortic rings. The relaxant effects of brazilin on isolated rat aortic rings were calculated as a percentage of the contraction in response to the second time of KCl (60 mmol/L). Data are expressed as mean±SEM. n=6. bP<0.05, cP<0.01 compared with control.
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fig3: Inhibitory effects of brazilin (25, 50, and 100 μmol/L) on concentration-response curves of NE (10−9–10−6 mol/L) (A and B) and KCl (10–60 mmol/L) (C and D) in endothelium-intact aortic rings. The relaxant effects of brazilin on isolated rat aortic rings were calculated as a percentage of the contraction in response to the second time of KCl (60 mmol/L). Data are expressed as mean±SEM. n=6. bP<0.05, cP<0.01 compared with control.

Mentions: In endothelium-intact aortic rings, pre-incubation with brazilin inhibited the concentration-response contraction of NE in a nonparallel fashion, and Emax declined with higher concentrations of brazilin. Brazilin (25, 50 and 100 μmol/L) depressed Emax to 127.22%±6.96%, 59.38%±10.17% and 0.91%±1.56%, respectively (vs control group 133.68%±5.58%, n=6) in endothelium-intact aortic rings (Figure 3A, B). We also observed that brazilin (25, 50 and 100 μmol/L) shifted the concentration-response curves of KCl to the right in a nonparallel fashion and depressed Emax to 86.66%±6.33%, 30.55%±4.68%, and 6.33%±1.51%, respectively (vs control group 90.37%±3.37%, n=6) in endothelium-intact aortic rings (Figure 3C, D). Compared with the above results (Figure 2), these results indicated that the relaxant effect of brazilin with pre-treatment is more potent than the effect with post-treatment.


Brazilin isolated from the heartwood of Caesalpinia sappan L induces endothelium-dependent and -independent relaxation of rat aortic rings.

Yan Y, Chen YC, Lin YH, Guo J, Niu ZR, Li L, Wang SB, Fang LH, Du GH - Acta Pharmacol. Sin. (2015)

Inhibitory effects of brazilin (25, 50, and 100 μmol/L) on concentration-response curves of NE (10−9–10−6 mol/L) (A and B) and KCl (10–60 mmol/L) (C and D) in endothelium-intact aortic rings. The relaxant effects of brazilin on isolated rat aortic rings were calculated as a percentage of the contraction in response to the second time of KCl (60 mmol/L). Data are expressed as mean±SEM. n=6. bP<0.05, cP<0.01 compared with control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4644902&req=5

fig3: Inhibitory effects of brazilin (25, 50, and 100 μmol/L) on concentration-response curves of NE (10−9–10−6 mol/L) (A and B) and KCl (10–60 mmol/L) (C and D) in endothelium-intact aortic rings. The relaxant effects of brazilin on isolated rat aortic rings were calculated as a percentage of the contraction in response to the second time of KCl (60 mmol/L). Data are expressed as mean±SEM. n=6. bP<0.05, cP<0.01 compared with control.
Mentions: In endothelium-intact aortic rings, pre-incubation with brazilin inhibited the concentration-response contraction of NE in a nonparallel fashion, and Emax declined with higher concentrations of brazilin. Brazilin (25, 50 and 100 μmol/L) depressed Emax to 127.22%±6.96%, 59.38%±10.17% and 0.91%±1.56%, respectively (vs control group 133.68%±5.58%, n=6) in endothelium-intact aortic rings (Figure 3A, B). We also observed that brazilin (25, 50 and 100 μmol/L) shifted the concentration-response curves of KCl to the right in a nonparallel fashion and depressed Emax to 86.66%±6.33%, 30.55%±4.68%, and 6.33%±1.51%, respectively (vs control group 90.37%±3.37%, n=6) in endothelium-intact aortic rings (Figure 3C, D). Compared with the above results (Figure 2), these results indicated that the relaxant effect of brazilin with pre-treatment is more potent than the effect with post-treatment.

Bottom Line: The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin.Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC.Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca(2+) channels.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing 100050, China.

ABSTRACT

Aim: Brazilin is one of the major constituents of Caesalpinia sappan L with various biological activities. This study sought to investigate the vasorelaxant effect of brazilin on isolated rat thoracic aorta and explore the underlying mechanisms.

Methods: Endothelium-intact and -denuded aortic rings were prepared from rats. The tension of the preparations was recorded isometrically with a force displacement transducer connected to a polygraph. The phosphorylation levels of ERK1/2 and myosin light chain (MLC) were analyzed using Western blotting assay.

Results: Application of brazilin (10-100 μmol/L) dose-dependently relaxed the NE- or high K(+)-induced sustained contraction of endothelium-intact aortic rings (the EC50 was 83.51±5.6 and 79.79±4.57 μmol/L, respectively). The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin. In addition, pre-incubation with brazilin dose-dependently attenuated the vasoconstriction induced by KCl, NE or Ang II. Pre-incubation with brazilin also markedly suppressed the high K(+)-induced extracellular Ca(2+) influx and NE-induced intracellular Ca(2+) release in endothelium-denuded aortic rings. Pre-incubation with brazilin dose-dependently inhibited the NE-stimulated phosphorylation of ERK1/2 and MLC in both endothelium-intact and -denuded aortic rings.

Conclusion: Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC. Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca(2+) channels.

Show MeSH
Related in: MedlinePlus