Long-term treatment with a Chinese herbal formula, Sheng-Mai-San, improves cardiac contractile function in aged rats: The role of Ca²⁺ homeostasis

A Chinese herbal formula Sheng-Mai-Yin (SMY), the liquid dosage form of Sheng-Mai-San, has been used clinically for treating heart failure, particularly in aged patients. To investigate the effect of SMY treatment on the contractile function of aged hearts, we first examined cardiac hemodynamics in aged rats. To define the mechanism involved in the enhancement of cardiac function, we investigated the effect of SMY treatment on Ca²⁺ homeostasis in ventricular cardiomyocytes isolated from aged rats. Ca²⁺ release was assessed by measurements of changes in cardiac Ca²⁺ transients and Ca²⁺ sparks, using laser scanning confocal microscopy. The functional status of Ca²⁺-release regulators, including L-type Ca²⁺ channels, sarcoplasmic reticulum (SR) Ca²⁺-adenosine triphosphatase (ATPase), and ryanodine receptors (RyRs), was also assessed. The results indicated that SMY treatment (2 g/kg per day for 30 doses within 6 weeks, intragastically) significantly improved hemodynamic parameters in aged rats. SMY treatment markedly increased the amplitude and shortened the duration of Ca²⁺ transients in aged cardiomyocytes, and reversed the age-related increase in frequency, decrease in amplitude, and changes in spatiotemporal properties of Ca²⁺ sparks in cardiomyocytes. In addition, SMY treatment increased the L-type Ca²⁺ current density, SR Ca ²⁺ content, and SR Ca²⁺-ATPase expression, and decreased the sensitivity of RyRs to Ca²⁺, all of which are causally related to increases in the amplitude of Ca²⁺ transients and the size of Ca²⁺ sparks. In conclusion, the improvement in cardiac contractile function afforded by SMY treatment in aged rats is likely mediated by an increase in Ca²⁺ release from the SR through L-type Ca²⁺ current-activated RyRs.