Synergistic effect of nicorandil and amlodipine on lysosomal hydrolases during experimental myocardial infarction in rats.
The synergistic effect of nicorandil (K(ATP) channel opener) and amlodipine (calcium channel blocker) on lysosomal hydrolases in serum and heart was examined by determining the activity of beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-galactosidase, cathepsin-D and acid phosphatase on isoproterenol-induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg(-1) daily, i.p.) for 2 d showed significant increase in serum and heart lysosomal hydrolases activity. Isoproterenol administration to rats resulted in decreased stability of the membranes, which was reflected by the lowered activity of cathepsin-D and beta-glucuronidase in mitochondrial, nuclear, lysosomal and microsomal fractions. Pretreatment with nicorandil (2.5 mg kg(-1) daily, p.o.) and amlodipine (5.0 mg kg(-1) daily, p.o.) for 3 d significantly prevented these alterations and restored the enzyme activity to near normal. These findings demonstrate that the pretreatment with nicorandil and amlodipine could preserve lysosomal integrity and hence establish the cardioprotective effect of the combination.
D000284:Administration, Oral; D017311:Amlodipine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006867:Hydrolases / Q000037:antagonists & inhibitors* / Q000097:blood; D007274:Injections, Intraperitoneal; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D020108:Nicorandil / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology
D004791:Enzyme Inhibitors; D017311:Amlodipine; D020108:Nicorandil; D006867:Hydrolases