Role of calcineurin in angiotensin II-induced cardiac myocyte hypertrophy of rats.
OBJECTIVE
The present study investigated the role of calcineurin in angiotensin II(AngII) -induced cardiac myocyte hypertrophy of rats.


METHODS
The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII-treated cardiomyocytes was tested by using PNPP; protein synethsis rate was assessed by 3H-leucine incorporation; atrial natriuretic factor(ANF) mRNA level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase (LDH) levels in cultured medium and by dyed cell numbers.


RESULTS
After stimulation of 10, 100 and 1 000 nmol/L of AngIi, calcineurin activities in the cardiomyocytes were increased by 13%, 57% (P < 0.05) and 228% (P < 0.01) respectively, compared with control group. Cyclosporin A(CsA), a specific inhibitor of calcineurin, markedly inhibited the calcineurin activity and decreased the 3H-leucine incorporation in AngII-treated cardiomyocytes in a dose-dependent manner. It was also found that CsA slightly reduced the mRNA level of ANF gene in AngII-stimulated cardiomyocytes.


CONCLUSIONS
During AngII-induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII-induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII-induced myocardial hypertrophy of rats.
Fu
M
M
Institute of Cardiovascular Research, First Hospital, Beijing Medical University, Beijing 100034.
Zhang
J
J
Xu
S
S
Pang
Y
Y
Liu
N
N
Tang
C
C
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis* / Q000235:genetics; D019703:Calcineurin / Q000378:metabolism / Q000502:physiology*; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D000804:Angiotensin II; D016572:Cyclosporine; D009320:Atrial Natriuretic Factor; D019703:Calcineurin