Pinocembrin inhibits angiotensin II-induced vasoconstriction via suppression of the increase of [Ca2+]i and ERK1/2 activation through blocking AT(1)R in the rat aorta

Li Li; Xiao-Bin Pang; Bai-Nian Chen; Li Gao; Le Wang; Shou-Bao Wang; Su-Bo Wang; De-Pei Liu; Guan-Hua Du

doi:10.1016/j.bbrc.2013.04.039

Pinocembrin inhibits angiotensin II-induced vasoconstriction via suppression of the increase of [Ca2+]i and ERK1/2 activation through blocking AT(1)R in the rat aorta

Biochem Biophys Res Commun. 2013 May 24;435(1):69-75. doi: 10.1016/j.bbrc.2013.04.039. Epub 2013 Apr 20.

Authors

Li Li¹, Xiao-Bin Pang, Bai-Nian Chen, Li Gao, Le Wang, Shou-Bao Wang, Su-Bo Wang, De-Pei Liu, Guan-Hua Du

Affiliation

¹ Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Xian Nong Tan Street, Beijing 100050, China.

PMID: 23611777
DOI: 10.1016/j.bbrc.2013.04.039

Abstract

Pinocembrin (5,7-dihydroxyflavanone) is one of the primary flavonoids in propolis. Angiotensin II (AngII) is a biologically active peptide that induces vasoconstriction via the activation of the angiotensin type 1 receptor (AT1R). In the present study, we investigated the vasorelaxant effect of pinocembrin on AngII-induced vasoconstriction and the molecular mechanism of action. Pinocembrin was observed to inhibit AngII-induced vasoconstriction in rat aortic rings with either intact or denuded endothelium. In endothelium-denuded tissues, pinocembrin (pD́'2pD2(') 4.28±0.15) counteracted the contractions evoked by cumulative concentrations of AngII. In a docking model, pinocembrin showed effective binding at the active site of AT1R. Pinocembrin was shown to inhibit both AngII-induced Ca(2+) release from internal stores and Ca(2+) influx. Moreover, the increase in the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and myosin light chain 2 (MLC2) induced by AngII was blocked by pinocembrin. These results demonstrate that pinocembrin inhibits AngII-induced rat aortic ring contraction, and these inhibitory effects may be related to the reduction of the AngII-induced increase in [Ca(2+)]i and ERK1/2 activation via blocking AT1R.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin II / pharmacology
Angiotensin II Type 1 Receptor Blockers / metabolism
Angiotensin II Type 1 Receptor Blockers / pharmacology
Animals
Aorta, Thoracic / cytology
Aorta, Thoracic / metabolism
Aorta, Thoracic / physiology*
Blotting, Western
Calcium / metabolism*
Cardiac Myosins / metabolism
Cells, Cultured
Dose-Response Relationship, Drug
Endothelium, Vascular / physiology
Enzyme Activation / drug effects
Extracellular Signal-Regulated MAP Kinases / metabolism*
Flavanones / metabolism
Flavanones / pharmacology*
In Vitro Techniques
Male
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Muscle, Smooth, Vascular / cytology
Muscle, Smooth, Vascular / metabolism
Myocytes, Smooth Muscle / drug effects
Myocytes, Smooth Muscle / metabolism
Myosin Light Chains / metabolism
Phosphorylation / drug effects
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1 / metabolism*
Vasoconstriction / drug effects*

Substances

Angiotensin II Type 1 Receptor Blockers
Flavanones
Myosin Light Chains
Receptor, Angiotensin, Type 1
myosin light chain 2
Angiotensin II
pinocembrin
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Cardiac Myosins
Calcium