Positive inotropic effect of atractylodin in normal rats and its underlying mechanism

doi:10.12047/j.cjap.5992.2020.087

Abstract

Abstract: Objective: To explore the positive inotropic effect of atractylodin which is major active component of Rhzoma Atractylodis Lanceae and its underlying mechanism. Methods: For in vivo study, six male SD rats were randomly selected for the heart pressure-volume loop (P-V loop) experiment. The effects of atractylodin (3 mg/kg, intraperitoneal injection) on hemodynamic parameters such as LVDP (left ventricular developed pressure), SW (stroke work), HR (heart rate), CO (cardiac output), SBP (systolic blood pressure) and DBP (diastolic blood pressure) were analyzed. For in vitro study, left ventricular developed pressure (LVDP) from the Langendroff-perfused isolated rat heart was analyzed before as the control and after atractylodin perfusion. For in vitro study, the effects of atractylodin and atractylodin with H89 (PKA inhibitor) or KN-93 (CaMKII inhibitor or Calyculin A (PP1, PP2A inhibitor) on LVDP were analyzed. The experiments were separated into four parts with six isolated hearts for each as follows: (1) Control→0.1→1→10 μmol/L atractylodin; (2) Control→200 nmol/L H89 (PKA inhibitor)→200 nmol/L H89+10 μmol/L atractylodin; (3) Control→500 nmol/L KN-93 (CaMKII inhibitor)→500 nmol/L KN-93+10 μmol/L atractylodin; (4) Control→10 nmol/L Calyculin A (PP1, PP2A inhibitor)→10 nmol/L Calyculin A+10 μmol/L atractylodin. For the study of rat left ventricular myocyte Ca²⁺ transient induced by field stimulation, the experiment design was the same as in vitro study. The six cells from the different rats were used for each part experiment. Results: ① Atractylodin (3 mg/kg) significantly increased the heart rate, cardiac output and stroke work (P＜0.05) and decreased the diastolic blood pressure (P＜0.05). ② Atractylodin (0.1, 1, 10 μmol/L) significantly increased the LVDP in a concentration dependent manner (P＜0.05). The positive inotropic effect of atractylodin could be blocked by PKA inhibitor H89. ③ Atractylodin (10 μmol/L) significantly increased the amplitude of SR Ca²⁺ transient amplitude mediated by facilitating sarcoplasmic reticulum SERCA2a. The enhanced amplitude of SR Ca²⁺ transient could be blocked by PKA inhibitor H89. Conclusion: Atractylodin had positive inotropic effect in rat heart both in vivo and in vitro with decreased diastolic blood pressure and its underlying mechanism was mediated by PKA. Based on the fact that the atractylodin exerted its positive inotropic effect was mediated by PKA, the PKA-SERCA2a signaling pathway might be the mechanism of the atractylodin's positive inotropy.

Key words: atractylodin, ghrelin receptor, positive inotropy, PKA, Ca²⁺ transient, SR SERCA2a, rat

CLC Number:

R969.4

GAO Li, ZHANG Wen-hui, WANG Yu-wei, ZHU Xiao-jia, XIAO Yu-jie, GAO Qian-wen, LI Wei, CHEN Long. Positive inotropic effect of atractylodin in normal rats and its underlying mechanism[J]. CJAP, 2020, 36(5): 408-413.

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