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

• Published in: Biochemical and biophysical research communications Vol. 435; no. 1; pp. 69 - 75
• Main Authors: Li, Li, Pang, Xiao-Bin, Chen, Bai-Nian, Gao, Li, Wang, Le, Wang, Shou-Bao, Wang, Su-Bo, Liu, De-Pei, Du, Guan-Hua
• Format: Journal Article
• Language: English
• Published: United States 24.05.2013
• Subjects: 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
• ISSN: 1090-2104
• DOI: 10.1016/j.bbrc.2013.04.039

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.