Modification of cardiac subcellular remodeling due to pressure overload by captopril and losartan.

:In view of the activation of renin-angiotensin system under conditions associated with pressure overload on the heart, we examined the effects of captopril, an angiotensin converting enzyme inhibitor, and losartan, an angiotensin II receptor antagonist, on cardiac function, myofibrillar ATPase and sarcoplasmic reticular (SR) Ca2+-pump (SERCA2) activities, as well as myosin and SERCA2 gene expression in hypertrophied hearts. Cardiac hypertrophy was induced in rats treated with or without captopril or losartan by banding the abdominal aorta for 8 weeks; sham operated animals served as control. Decrease in left ventricular developed pressure, +dP/dt and -dP/dt as well as increase in left ventricular end diastolic pressure and increased muscle mass due to pressure overload were prevented by captopril or losartan. Treatment of animals with captopril or losartan also attenuated the pressure overload-induced depression in myofibrillar Ca2+-stimulated ATPase, myosin ATPase, SR Ca2+-uptake and SR Ca2+-release activities. An increase in beta-myosin heavy chain mRNA and a decrease in alpha-myosin heavy chain mRNA as well as depressed SERCA2 protein and SERCA2 mRNA levels were prevented by captopril or losartan. These results suggest that both captopril and losartan improve myocardial function in cardiac hypertrophy by preventing changes in gene expression and subsequent subcellular remodeling due to pressure overload.

Liu X ，Sentex E ，Golfman L ，Takeda S ，Osada M ，Dhalla NS ... -  《CLINICAL AND EXPERIMENTAL HYPERTENSION》

Captopril treatment improves the sarcoplasmic reticular Ca(2+) transport in heart failure due to myocardial infarction.

:Although captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been shown to exert a beneficial effect on cardiac function in heart failure, its effect on the status of sarcoplasmic reticulum (SR) Ca(2+) transport in the failing heart has not been examined previously. In order to determine whether captopril has a protective action on cardiac function, as well as cardiac SR Ca(2+)-pump activity and gene expression, a rat model of heart failure due to myocardial infarction was employed in this study. Sham operated and infarcted rats were given captopril (2 g/l) in drinking water; this treatment was started at either 3 or 21 days and was carried out until 8 weeks after the surgery. The untreated animals with myocardial infarction showed increased heart weight and elevated left ventricular end diastolic pressure, reduced rates of pressure development and pressure fall, as well as depressed SR Ca(2+) uptake and Ca(2+)-stimulated ATPase activities in comparison with the sham control group. These hemodynamic and biochemical changes in the failing hearts were prevented by treatment of the infarcted animals with captopril. Likewise, the observed reductions in the SR Ca(2+) pump and phospholamban protein contents, as well as in the mRNA levels for SR Ca(2+) pump ATPase and phospholamban, in the failing heart were attenuated by captopril treatment. These results suggest that heart failure is associated with a defect in the SR Ca(2+) handling and a depression in the gene expression of SR proteins; the beneficial effect of captopril in heart failure may be due to its ability to prevent remodeling of the cardiac SR membrane.

Shao Q ，Ren B ，Zarain-Herzberg A ，Ganguly PK ，Dhalla NS ... -  《JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY》

Inhibition of beta-myosin heavy chain gene expression in pressure overload rat heart by losartan and captopril.

Ling Q ，Chen TH ，Guo ZG 《-》

Influence of long-term treatment of imidapril on mortality, cardiac function, and gene expression in congestive heart failure due to myocardial infarction.

Ren B ，Shao Q ，Ganguly PK ，Tappia PS ，Takeda N ，Dhalla NS ... -  《CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY》

[Effects of losartan, ramipril and their combination on left ventricular remodeling and function in spontaneous hypertensive rats].

Xu R ，Zhang Y ，Zhang M ，Li XC ，Cai H ，Chen WQ ，Zhu H ，Ge ZM ，Zhang W ... -  《-》