98. Long-term treatment with a Chinese herbal formula,Sheng-Mai-San, improves cardiac contractile function in aged rats: the role ofCa2+ homeostasis.

Zhang GQ[1], Yu ZL[2], Liu WT[3], Wang H[2], Fong WF[2], Tang LM[4], Xiong YH[4], Ko KM[5].

[1] Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
[2] School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
[3] Department of Pharmacology, Nanjing Medical University, Nanjing, China.
[4] Laboratory for Quality Control, Jiangxi Jurentang Pharmaceutical Co. Ltd., Nanchang, China.
[5] Department of Biochemistry,Hong Kong University of Science& Technology, Clear Water Bay,Hong Kong, China

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 Ca2+ 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.