Sub-antihypertensive doses of ramipril normalize sarcoplasmic reticulum calcium ATPase expression and function following cardiac hypertrophy in rats.
We examined the hypothesis that the angiotensin converting enzyme inhibitor ramipril at sub-antihypertensive concentrations could improve sarcoplasmic reticulum (SR) CaATPase expression and function in compensated hypertrophied rat hearts. Five weeks after abdominal aortic constriction, rats received a daily dose (50 micrograms/kg/day) of ramipril or vehicle for 4 weeks. Cardiac angiotensin-converting enzyme (ACE) activity increased with cardiac hypertrophy (CH) but returned to normal following ramipril treatment. SR CaATPase protein levels and activity decreased with CH (P < 0.05) and were normalized following ramipril treatment (P < 0.05 for protein and activity). No change in phospholamban (PLB) protein levels could be demonstrated between any of the groups. In contrast, ramipril treatment specifically increased control SR CaATPase and PLB mRNA levels by > 60% (P < 0.01) and > 30%, respectively. In the hypertrophied group, SR CaATPase increased by 35% (P < 0.05 n = 6) after ramipril treatment. Calsequestrin mRNA levels were unaffected by ramipril administration. In conclusion, ramipril normalizes SR CaATPase protein expression and function in pressure-overloaded and compensated CH. The effects of ramipril are however multifaceted, affecting RNA and protein expression differentially.
Boateng
S Y
SY
Imperial College School of Medicine, Department of Cardiothoracic Surgery, London, UK.
Seymour
A M
AM
Bhutta
N S
NS
Dunn
M J
MJ
Yacoub
M H
MH
Boheler
K R
KR
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000378:metabolism* / Q000494:pharmacology; D002155:Calsequestrin / Q000494:pharmacology; D006332:Cardiomegaly / Q000201:enzymology*; D002339:Carotid Arteries / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006157:Guanosine Monophosphate / Q000652:urine; D015151:Immunoblotting; D008297:Male; D010070:Oxalates / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011312:Pressure; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D000099211:Phospholamban