Modification of Cardiac Subcellular Remodeling Due to Pressure Overload by Captopril and Losartan

Abstract

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 Icsartan 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 β-myosm heavy chain mRNA and a decrease in α-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.

Key Words:

• Cardiac hypertrophy
• cardiac gene expression
• heart function
• myofibrillar ATPase
• sarcoplasmic reticular Ca²⁺-pump