Mechanisms underlying the cardioprotective effect of Salvianic acid A against isoproterenol-induced myocardial ischemia injury in rats: Possible involvement of L-type calcium channels and myocardial contractility

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• 作者：Qiongtao Song^a ; Xi Chu^b ; Xuan Zhang^c ; Yifan Bao^d ; Yuanyuan Zhang^c ; Hui Guo^c ; Yang Liu^a ; Hongying Liu^e ; Jianping Zhang^c ; Ying Zhang^c ; Li Chu^a ; ^c ; ^{chuli0614@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ATP ; adenosine triphosphate ; CK ; creatine kinase ; Con ; Control ; H&E ; hematoxylin and eosin ; H-SAA ; high-dose Salvianic acid A ; ICa-L ; L-type calcium current ; IHD ; ischemic heart disease ; ISO ; isoproterenol ; LDH ; lactate dehydrogenase ; L-SAA ; low-dose Salvianic acid A ; LTCCs ; L-type calcium channels ; SAA ; Salvianic acid A ; VER ; Verapamil
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：2 August 2016
• 年：2016
• 卷：189
• 期：Complete
• 页码：157-164
• 全文大小：1715 K

文摘

Salvianic acid A (SAA), which is the main water-soluble fraction in Radix Salviae Milthiorrhizae, has been widely applied for treating cardiovascular diseases in China.

Aim of the study

To explore the effects of SAA against myocardial ischemia injury induced by isoproterenol (ISO) in rats and to clarify its underlying myocardial protective mechanisms based on l-type calcium channels and myocardial contractility.

Materials and methods

The myocardial ischemia injured rat model was induced by administering ISO (85 mg/kg) subcutaneously at evenly spaced intervals throughout the day and night for 2 consecutive days. Serum cardiac biomarkers were analyzed, and heart tissues were isolated and prepared for histopathology assay. The regulatory effects of SAA on the L-type calcium current (I_Ca-L) in rat ventricular myocytes were observed by the patch clamp technique. The IonOptix Myocam detection system was used to observe the contractility of isolated rat ventricular myocytes.

Results

SAA significantly ameliorated changes in heart morphology and electrocardiographic patterns and reduced serum levels of creatine kinase and lactate dehydrogenase in the ISO-induced myocardial ischemia injured rat model. Meanwhile, SAA reduced I_Ca-L in a concentration-time dependent way with an IC₅₀ of 1.47×10⁻⁵ M, upshifted the current-voltage, activation, and inactivation curves of I_Ca-L, and significantly inhibited the amplitude of the cell shortening.

Conclusions

These results indicate that SAA exhibits significant cardioprotective effects against the ISO-induced myocardial ischemia injury, potentially through inhibiting I_Ca-L and decreasing myocardial contractility.