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The objective of the present study was to evaluate the cardiovascular protective effects of Danshensu, a water-soluble active component of Danshen, in spontaneously hypertensive rats (SHR). SHR (male, 9 weeks old, n‫؍‬ ‫)03؍‬ were divided into three groups: 1) saline control (n‫؍‬ ‫;)01؍‬ 2) a Danshensu (10 mg/kg/d, intraperitoneally (i.p.)) treatment group (n‫؍‬ ‫;)01؍‬ and 3) a Valsartan (10 mg/kg/d, intragastrically (i.g.)) treatment group (n‫؍‬ ‫.)01؍‬ Age-matched Wistar-Kyoto rats (n‫؍‬ ‫)01؍‬ were used as normotensive controls. Saline and drug treatments were administered for 6 weeks. When the rats were 15 weeks old, their hearts were excised and arrhythmias were induced by an ex vivo ischemia/reperfusion protocol. The heart weight to body weight index was significantly increased in SHR, and this increase was attenuated with Danshensu treatment (both pϽ Ͻ0.05). Systolic blood pressure and diastolic blood pressure were also decreased with Danshensu treatment, from 145؎ ؎3 and 103؎ ؎10 mmHg to 116؎ ؎7 and 87؎ ؎2 mmHg in SHR and Danshensu-treated groups, respectively (both pϽ Ͻ0.05). The incidences of ventricular tachycardia and ventricular fibrillation decreased from 100 to 50% and 30% in SHR, respectively, with Danshensu treatment (both pϽ Ͻ0.05). Serum nitric oxide content and inducible nitric oxide synthase activity were significantly increased with Danshensu (both pϽ Ͻ0.05). In addition, Danshensu increased the K ؉ ؉ current density and Ca 2؉ ؉ activated K ؉ ؉ channel current density of mesenteric vascular smooth muscle cells isolated from SHRs. Together, these results demonstrate that Danshensu imparts cardiovascular protection by modifying vascular responses during the progression of hypertension.

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In the present study, the potential antiarrhythmic activities of a new multiple ion channel blocker, CPUY11018 (Y18) were investigated. The effects of Y18 on ICa,L and INa were studied using whole-cell patch clamp techniques in ventricular muscle cells from normal rats and guinea pigs. The antiarrhythmic effects were tested using a rat model of aconitine-induced arrhythmias. The effects of Y18 on induction of QT prolongation and torsades de pointes (TdP) were investigated in anesthetized rabbits during stimulation with methoxamine. Y18 produced a concentration-dependent inhibition of ICa,L and INa in rat ventricular myocytes with IC50 values of 88 mmol/l and 6.5 mmol/l, respectively. In the Y18 treatment group, the development of arrhythmias was significantly delayed. Doses of aconitine that induced ventricular fibrillation were decreased following treatment with 6 mg/kg Y18 (3.8 Ϯ 0.4 mg/100 g vs 6.2 Ϯ 1.3 mg/kg). A significant decrease in the occurrence of atrial fibrillation (100% to 33%; P < 0.05) occurred following Y18 administration. Y18 induction of TdP was significantly less than that seen with dofetilide and azimilide (Az). Thus, Y18 significantly inhibited the production of aconitine-induced arrhythmias with a low potency for TdP induction. These results suggest that Y18 is a multiple channel blocker with promising antiarrhythmic potential. Drug Dev Res 73 : 214-221, 2012.