Hydroxysafflor yellow A actives BK(Ca) channels and inhibits L-type Ca channels to induce vascular relaxation.

Hydroxy-safflor yellow A (HSYA) can exert a variety of effects upon the vascular system. However, the underlying mechanisms are not clear. The present study is to investigate its vasodilating effect and the mechanisms. Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were enrolled for studying effects of HSYA on blood pressure, vasodilation, intracellular Ca2+ transient and membrane ion channels. Vasodilation and intracellular Ca2+ transient were measured by using vasomotor assay and fluorescence imaging system, respectively. The effect of HSYA on the large conductance Ca2+ activated and voltage-gated potassium channel (BKCa channel) currents in rat mesentery artery and on L-type calcium channel (Ca-L) currents in HEK293cells expressed with Ca-L were investigated using patch clamp techniques. Blood pressure of SHR and WKY rats were concentration dependently reduced by HSYA with a larger effect of HSYA in SHR than that in WKY rats. The tension of mesenteric arteries induced by 3 μM phenylephrine was attenuated by HSYA (IC50 = 90.8 μΜ). Patch clamp study showed that HSYA could activate BKCa channels and suppress Ca-L channels in a concentration dependent manner. The results of calcium signaling assays indicated that HSYA could reduce the intracellular free Ca2+ level. These findings demonstrate that HSYA could activate BKCa channels and inhibit Ca-L channels and reduce intracellular free Ca2+ level, which are probably important for its vasodilatory effect.

Wang N ，He D ，Zhou Y ，Wen J ，Liu X ，Li P ，Yang Y ，Cheng J ... -  《-》

Calcium exerts a larger regulatory effect on potassium+ channels in small mesenteric artery mycoytes from spontaneously hypertensive rats compared to Wistar-Kyoto rats.

Cox RH ，Lozinskaya I ，Dietz NJ 《AMERICAN JOURNAL OF HYPERTENSION》

Ramipril treatment alters Ca(2+) and K(+) channels in small mesenteric arteries from Wistar-Kyoto and spontaneously hypertensive rats.

Cox RH ，Lozinskaya I ，Matsuda K ，Dietz NJ ... -  《AMERICAN JOURNAL OF HYPERTENSION》

The vascular dilatation induced by Hydroxysafflor yellow A (HSYA) on rat mesenteric artery through TRPV4-dependent calcium influx in endothelial cells.

Hydroxysafflor yellow A (HSYA) is the principal constituent of the flowers of Carthamus tinctorius L., a traditional Chinese herbal medicine, which has been used for the treatment of cerebrovascular and cardiovascular diseases due to its property of promoting blood circulation and removing blood stasis. It is dominated in the water extract of Carthamus tinctorius L., which has been used in the clinical treatment for cardiovascular diseases. HSYA exerts a variety of pharmacological efficacy upon the vascular system. However, the underlying mechanisms remain unclear. To investigate the vascular dilatation effect of HSYA on rat mesenteric artery (MA) and its potential mechanism. Adult male Wistar rats were applied to the study. Tension studies were conducted to determine the dilatation activity of HSYA against pre-contracted mesenteric arterial (MA) rings by U 46619 and Phenylephrine (PE). The vascular activities were measured with or without incubation with some selective inhibitors, including L-N(ω)-nitro-L-arginine methyl ester (L-NAME, a nitro oxide synthase inhibitor), HC-067047 (a selective TRPV4 antagonist), BaCl2 (a Kir channel blocker), and Indomethacin (Indo, a nonselective cyclooxygenase inhibitor), respectively. Immunocytochemistry, Calcium Imaging, NO Production detection, and Western Blot were also employed to further study the underlying mechanism. HSYA reversed the constriction of MAs induced by U 46619 in a manner of concentration dependency, and the dilatation capability was reversed by L-NAME. This effect was significantly dependent on the intactness of MA endothelium, accompanying an increment of NO production in mesenteric arterial endothelium cells. The increment of NO production was reversed by inhibiting the PKA. Also, the expression of p-eNOS was activated by HSYA shown in Western Blot assays. The cells imaging revealed a significant increase and drop of the influx of Ca2+ before and after treatment with HC-067047. These findings suggest that HSYA exerts vessel dilation effect on MAs via a TRPV4-dependent influx of Ca2+ in endothelium cells, PKA-dependent eNOS phosphorylation and NO production mechanism. The present study indicates that HSYA has the potential to be a future candidate for the treatment of hypertension.

Yang J ，Wang R ，Cheng X ，Qu H ，Qi J ，Li D ，Xing Y ，Bai Y ，Zheng X ... -  《-》

The effects of hydroxysafflor yellow A on blood pressure and cardiac function.

This work aims to investigate the effects of HSYA on cardiac function and blood pressure. To evaluate changes in mean arterial pressure (MAP) and heart rate (HR), different groups of pentobarbitone-anesthetized normotensive and spontaneously hypertensive rats (SHR) were treated with intravenous HSYA (0.1-3 mg/kg). Isolated WKY rat hearts in Langendorff system were employed for examining the effect of HSYA on hemodynamic. After 30 min equilibration time the isolated hearts were perfused with HSYA (30 μmol/L) in a stepwise fashion. Potassium channel inhibitors were used to determine the role of potassium channel activation in HSYA effect. Intravenous injection of the HSYA significantly reduced MAP and HR in both normotensive rats and SHR in a dose-dependent manner. HSYA reduced left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum rate of increase of left ventricular pressure (+dp/dt(max)) and heart rate (HR) in a dose-dependent manner. HSYA had no remarkable effect on the maximum rate of decrease of left ventricular pressure (-dp/dt(max)); BK(Ca) and K(ATP) blocker can weakened the inhibitory effect of HSYA on heart function and HR, but K(V) and K(ACh) blocker did not significantly weaken the HSYA effects. Our results show that HSYA could significantly reduce blood pressure and heart rate, which may be related to activation of BK(Ca) and K(ATP) channels.

Nie PH ，Zhang L ，Zhang WH ，Rong WF ，Zhi JM ... -  《-》