Long-term treatment with a Chinese herbal formula, Sheng-Mai-San, improves cardiac contractile function in aged rats: the role of Ca(2+) 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 Ca(2+) homeostasis in ventricular cardiomyocytes isolated from aged rats. Ca(2+) release was assessed by measurements of changes in cardiac Ca(2+) transients and Ca(2+) sparks, using laser scanning confocal microscopy. The functional status of Ca(2+)-release regulators, including L-type Ca(2+) channels, sarcoplasmic reticulum (SR) Ca(2+)-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 Ca(2+) transients in aged cardiomyocytes, and reversed the age-related increase in frequency, decrease in amplitude, and changes in spatiotemporal properties of Ca(2+) sparks in cardiomyocytes. In addition, SMY treatment increased the L-type Ca(2+) current density, SR Ca(2+) content, and SR Ca(2+)-ATPase expression, and decreased the sensitivity of RyRs to Ca(2+), all of which are causally related to increases in the amplitude of Ca(2+) transients and the size of Ca(2+) sparks. In conclusion, the improvement in cardiac contractile function afforded by SMY treatment in aged rats is likely mediated by an increase in Ca(2+) release from the SR through L-type Ca(2+) current-activated RyRs.
Zhang
Guang-Qin
GQ
Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Wang
Hui
H
Liu
Wen-Tao
WT
Dong
Hang
H
Fong
Wang-Fun
WF
Tang
Li-Min
LM
Xiong
Yun-Hua
YH
Yu
Zhi-Ling
ZL
Ko
Kam-Ming
KM
D000375:Aging; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D006706:Homeostasis; D018613:Microscopy, Confocal; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism
D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D019837:Ryanodine Receptor Calcium Release Channel; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium