Protective action of lacidipine in cardiac hypertrophy of the spontaneously hypertensive stroke-prone rat: an ultrastructural study.
We investigated the effect on cardiac hypertrophy of a once-daily treatment with lacidipine, at doses that do not reduce systolic blood pressure. Spontaneously hypertensive stroke-prone rats (SHR-SP) were fed a 1% NaCl enriched diet and treated daily by gastric gavage with lacidipine at doses of 0.3, 1, or 3 mg/kg/die or vehicle. At 15 weeks of age the rats were sacrificed. The heart was removed, weighed and processed for transmission electron microscopy, scanning electron microscopy and ultrastructural morphometry. Though the treatment did not reduce systolic blood pressure, heart weight and heart weight/body weight ratio were lower in the lacidipine-treated rats than in those treated with vehicle alone. Medial and subendothelial lesions were visible in coronaries of vehicle-treated SHR-SP but not in animals treated with lacidipine. In the cardiocytes of the lacidipine-treated rats, the myofibrils had a more regular arrangement and the intercalated discs did not show the irregular course and infoldings seen in the vehicle-treated rats. Morphometry showed a significantly higher density of mitochondria in the cardiocytes of lacidipine-treated SHR-SP. Scanning electron microscopy identified a decrease in the width of cardiocytes and in the number and length of lateral branches following lacidipine-treatment. The cardio-protective action of this calcium-antagonist at doses that do not reduce systolic blood pressure is attributable both to its vascular activity and to improvement in cytoplasmic organization of cardiocytes.
Cristofori
P
P
Glaxo Research Laboratories, Glaxo S.p.A, Verona, Italy.
Sbarbati
A
A
Accordini
C
C
Terron
A
A
Micheli
D
D
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D006332:Cardiomegaly / Q000188:drug therapy* / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D003331:Coronary Vessels / Q000648:ultrastructure; D004095:Dihydropyridines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009206:Myocardium / Q000648:ultrastructure; D051381:Rats; D011918:Rats, Inbred SHR
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine