RUMEX ACETOSAL. INDUCES VASORELAXATION IN RAT AORTA VIA ACTIVATION OF PI3-KINASE/Akt- AND Ca2+-eNOS-NO SIGNALING INENDOTHELIAL CELLS

The endothelium plays an important role in the control of vascular tone (1). Several endothelium-dependent vasodilators, such as bradykinin, acetylcholine and histamine, have been reported to elevate Ca 2+ level in endothelial cells, and activate the synthesis and release of endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO) and prostacyclin (PGI2) (2), which lead to vasorelaxation (3). In blood vessels, endothelial nitric oxide synthase (eNOS) converts L-ar ginine to L-citrulline and NO. In addition, NO generation by eNOS depends on Ca 2+/calmodulin-dependent and also Ca2+/calmodulin-independent signaling pathways (4). Furthermore, the catalytic activity of eNOS is modulated by phosphorylation at multiple sites (5). The phosphorylation on Ser1177 is associated with the activation of eNOS in response to various stimuli. Several studies have reported that quercetin, Ca2+/calmodulin-dependent protein kinase II and AMP-activated protein kinase (AMPK) activate the phosphorylation of eNOS at Ser1179, thus increasing NO release (6-8) through protein kinase B (Akt) (9), PI3-kinase/Akt (10) and PKA(8) in endotheliumdependent vasomotion. Rumex acetosa L. (Polygonaceae) (RA) is a perennial herb that is widely distributed in areas with temperate climate and the aerial part of this plant has been used traditionally for treatment of skin irritations and diarrhoea. Modern phytotherapeutical preparations with nationally registered drug status in Europe contain extracts from RAfor treatment of acute and chronic infections of the upper respiratory system (1 1). It has been reported that the aerial parts of RAcontain hyperin, proanthocyanidin and phloroglucinol derivative beside dif ferent flavonoids, such as emodin and chrysophanol (12-14), some of which exhibited many pharmacological ef fects including heatcleaning, diuretic, anti-oxidative, anti-hypertensive, antimicrobial, and anticancer ef f ct (13-17). However , to the best of our knowledge, the ef f ct of RA on the vasorelaxant activity has not yet been defined. For this purpose, the present study was to investigate the vasorelaxant ef fects of ethanol JOURNALOF PHYSIOLOGYAND PHARMACOLOGY 2015, 66, 6, 907-915