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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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Role of K+ channels in the vasodilatory effect of brazilin in endothelium-denuded aortic rings. Pre-incubation of glibenclamide (10 μmol/L), TEA (5 mmol/L) and 4-AP (100 μmol/L) did not have significant effect on brazilin induced relaxation in endothelium-denuded aorta rings pre-contracted by NE (1 μmol/L). The relaxant effects of brazilin on isolated rat aortic rings were calculated as a percentage of the contraction in response to NE (1 μmol/L). Data are expressed as mean±SEM. n=6.
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fig6: Role of K+ channels in the vasodilatory effect of brazilin in endothelium-denuded aortic rings. Pre-incubation of glibenclamide (10 μmol/L), TEA (5 mmol/L) and 4-AP (100 μmol/L) did not have significant effect on brazilin induced relaxation in endothelium-denuded aorta rings pre-contracted by NE (1 μmol/L). The relaxant effects of brazilin on isolated rat aortic rings were calculated as a percentage of the contraction in response to NE (1 μmol/L). Data are expressed as mean±SEM. n=6.

Mentions: In endothelium-denuded rings, pretreatment with TEA (5 mmol/L), glibenclamide (10 μmol/L) and 4-AP (100 μmol/L) did not remarkably affect brazilin-induced vasorelaxation, with Emax of 46.63%±7.25%, 62.1%±1.9%, and 58.7%±2.5%, respectively (vs control group 51.53%±5.66%, n=6, Figure 6).


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)

Role of K+ channels in the vasodilatory effect of brazilin in endothelium-denuded aortic rings. Pre-incubation of glibenclamide (10 μmol/L), TEA (5 mmol/L) and 4-AP (100 μmol/L) did not have significant effect on brazilin induced relaxation in endothelium-denuded aorta rings pre-contracted by NE (1 μmol/L). The relaxant effects of brazilin on isolated rat aortic rings were calculated as a percentage of the contraction in response to NE (1 μmol/L). Data are expressed as mean±SEM. n=6.
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Related In: Results  -  Collection

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

fig6: Role of K+ channels in the vasodilatory effect of brazilin in endothelium-denuded aortic rings. Pre-incubation of glibenclamide (10 μmol/L), TEA (5 mmol/L) and 4-AP (100 μmol/L) did not have significant effect on brazilin induced relaxation in endothelium-denuded aorta rings pre-contracted by NE (1 μmol/L). The relaxant effects of brazilin on isolated rat aortic rings were calculated as a percentage of the contraction in response to NE (1 μmol/L). Data are expressed as mean±SEM. n=6.
Mentions: In endothelium-denuded rings, pretreatment with TEA (5 mmol/L), glibenclamide (10 μmol/L) and 4-AP (100 μmol/L) did not remarkably affect brazilin-induced vasorelaxation, with Emax of 46.63%±7.25%, 62.1%±1.9%, and 58.7%±2.5%, respectively (vs control group 51.53%±5.66%, n=6, Figure 6).

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