Dysfunction of myocardial sarcoplasmic reticulum in rats with myocardial calcification.
We investigated the relationship between cardiac dysfunction and Ca2+ transport in the myocardial sarcoplasmic reticulum (SR) during the pathogenesis of cardiovascular calcification in rats. The possible mechanism of SR dysfunction was explored by detecting the alteration of the nitric oxide/nitric oxide synthase (NO/NOS) pathway in the SR. Using the vitamin D plus nicotine (VDN treatment for 2 week and 6 week) experimental model of cardiac calcification, cardiac function and sarcoplasmic reticulum function were measured. Inhibition of cardiac functions in vivo (peak rate of contraction and peak rate of relaxation, P < 0.05 or P < 0.01) were observed in all calcification groups, simultaneously, Ca2+ release and uptake in the SR as well as the Ca2+ release channel and Ca2+ pump activity were inhibited. Myocardial Ca2+ concentration and cardiac and SR dysfunction were inversely related (P < 0.05). The specific NO/NOS pathway (NO production, NOS activity and nNOS expression in the SR) was upregulated in the SR and associated with calcification (both 2- and 6 week VDN groups). These results indicate that cardiac dysfunction associated with myocardial calcification might be mediated by SR dysfunction, which may result from an impaired SR-specific NO/NOS pathway.
Bin
Geng
G
Institute of Cardiovascular Research, Peking University First Hospital, Beijing, 100034, China.
Fen
Qi Yong
QY
Hua
Liu Xiu
LX
Hong
Zhang Bao
ZB
Zheng
Pang Yong
PY
Shu
Tang Chao
TC
D000818:Animals; D002114:Calcinosis / Q000139:chemically induced / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000139:chemically induced / Q000503:physiopathology*; D002762:Cholecalciferol; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology*; D008297:Male; D009538:Nicotine; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D015854:Up-Regulation
D019837:Ryanodine Receptor Calcium Release Channel; D002762:Cholecalciferol; D009569:Nitric Oxide; D009538:Nicotine; D019001:Nitric Oxide Synthase; D002118:Calcium