Liu X, Sentex E, Golfman L, Takeda S, Osada M, Dhalla N S
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Department of Physiology, University of Manitoba, Winnipeg, Canada.
Clin Exp Hypertens. 1999 Jan-Feb;21(1-2):145-56. doi: 10.3109/10641969909068657.
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.
鉴于在与心脏压力超负荷相关的条件下肾素 - 血管紧张素系统的激活，我们研究了血管紧张素转换酶抑制剂卡托普利和血管紧张素II受体拮抗剂氯沙坦对肥厚心脏的心脏功能、肌原纤维ATP酶和肌浆网（SR）Ca2 + - 泵（SERCA2）活性以及肌球蛋白和SERCA2基因表达的影响。通过结扎腹主动脉8周，在接受或未接受卡托普利或氯沙坦治疗的大鼠中诱导心脏肥大；假手术动物作为对照。卡托普利或氯沙坦可预防因压力超负荷导致的左心室舒张末压降低、+dP/dt和 -dP/dt降低以及左心室舒张末压升高和肌肉质量增加。用卡托普利或氯沙坦治疗动物也减轻了压力超负荷引起的肌原纤维Ca2 +刺激的ATP酶、肌球蛋白ATP酶、SR Ca2 +摄取和SR Ca2 +释放活性的降低。卡托普利或氯沙坦可预防β - 肌球蛋白重链mRNA增加、α - 肌球蛋白重链mRNA减少以及SERCA2蛋白和SERCA2 mRNA水平降低。这些结果表明，卡托普利和氯沙坦均可通过防止因压力超负荷导致的基因表达变化和随后的亚细胞重塑来改善肥厚心脏的心肌功能。
