Chenodeoxycholic and deoxycholic acids induced positive inotropic and negative chronotropic effects on rat heart

Bile acids are endogenous amphiphilic steroids from the metabolites of cholesterol. Studies showed that they might contribute to the pathogenesis of cardiopathy in cholestatic liver diseases. Chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) is associated with colon cancer, gallstones, and gastrointestinal disorders. However, little information is available regarding their cardiac effects. Here, we reported that CDCA (100 mu M) and DCA (100 mu M) significantly increased the left ventricular developed pressure of the isolated rat hearts to 122.3 +/- 5.6% and 145.1 +/- 13.7%, and the maximal rate of the pressure development rising and descending (+/- dP/dt(max)) to 103.4 +/- 17.6% and 124.4 +/- 37.7% of the basal levels, respectively. They decreased the heart rate and prolonged the RR, QRS, and QT intervals of Langendorff-perfused hearts in a concentration-dependent manner. Moreover, CDCA and DCA increased the developed tension of left ventricular muscle and the cytosolic Ca(2+)concentrations in left ventricular myocytes; these functions positively coordinated with their inotropic effects on hearts. Additionally, CDCA (150 mu M) and DCA (100 mu M) decreased the sinoatrial node beating rate to 80.6 +/- 3.0% and 79.7 +/- 0.9% of the basal rate (334.2 +/- 10.7 bpm), respectively. These results were consistent with their chronotropic effects. In conclusion, CDCA and DCA induced positive inotropic effects by elevating the Ca(2+)in left ventricular myocytes. They exerted negative chronotropic effects by lowering the pace of the sinoatrial node in rat heart. These results indicated that the potential role of bile acids in cardiopathy related to cholestasis.