Biochemical, structural and ultrastructural changes in the Prague hereditary hypercholesterolemic (PHHC) rats heart after the long treatment with calcium channel blockers.
Elevated plasma cholesterol concentration may be important in the initiation of heart ischemia and progression of atherogenesis. It has been shown that drugs affecting calcium entry into cells can attenuate the development of this cholesterol induced changes. The aim of this work was to study the influence of five calcium channel blockers 6 weeks treatment on some parameters of lipid metabolism, morphological and ultrastructural changes in the Prague hereditary hypercholesterolemic (PHHC) rats myocardium. The calcium antagonists were administered twice daily perorally in the following doses: nifedipine and nitrendipine 0.2 mg.kg-1, nimodipine 2.5 mg.kg-1, verapamil and diltiazem 1.0 mg.kg-1 body weight. Cholesterol diet decreased the level of free fatty acids significantly (from 5.59 +/- 0.216 to 3.83 +/- 0.371 mumol.g-1), increased the level of total cholesterol (from 28.0 +/- 1.92 to 34.0 +/- 2.90 mumol.g-1) and caused micronecrosis. Examination of myocardial ultrastructure showed a frequent occurrence of lysosomes as well as large numerous autophagic vacuoles and contracture bands of myofibrils. These effects were partly suppressed by calcium channel blockers verapamil and diltiazem, but dihydropyridines were not effective. Observed biochemical changes were in accordance with structural and ultrastructural investigations.
Edelsteinova
S
S
Department of Pharmacology, Pharmaceutical Faculty, Comenius University, Bratislava, Slovakia.
Svec
P
P
Augustiniová
B
B
Devecka
V
V
Pazin-Hrickova
E
E
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D005230:Fatty Acids, Nonesterified; D002784:Cholesterol