Decreased vasodilatory effect of tanshinone IIA Sodium Sulfonate on mesenteric artery in hypertension

Abstract Tanshinone ⅡA Sodium Sulfonate (DS-201), a derivative of traditional Chinese medicinal herb Danshen, has been clinically used for various cardiovascular diseases. Previous studies showed that DS-201 induced vascular relaxation partly due to the activation of the large conductance Ca 2+ -activated potassium (BK Ca ) channels. However, the efficacy of DS-201 on the resistant vessels in hypertension remains unknown. Mesentery arteries obtained from spontaneously hypertensive rats (SHR) and hypertension patients were used in this study. The endothelium-denuded mesenteric arteries were prepared to measure the artery tension and evaluate the vasodilatory effect of DS-201. The results showed that DS-201 had a vasodilatory effect on the mesenteric artery rings pre-contracted with either phenylephrine (PE) or thromboxane mimetic U46619 in a concentration-dependent manner. However, the vasodilatory effect of DS-201 significantly decreased in hypertension than in control arteries due to a decrease in protein level of BK Ca β1subunit. A BK Ca channel blocker IbTX (200 nM) significantly inhibited the relaxant effect of DS-201 on non-hypertensive arteries, whereas the BK Ca channel specific agonist NS1619 rescued the vasodilating effects of DS-201 on hypertensive vessels. These results indicate that the vasodilating effect of DS-201 is BK Ca -dependent. This study demonstrated that DS-201 alone may not be effective for treating hypertension, but it may be considered as therapy combined with BK Ca -agonists or methods rescuing BK Ca functions.