Both D-cis- and L-cis-diltiazem attenuate hydrogen peroxide-induced derangements in rat hearts.
The effects of D-cis- and L-cis-diltiazem on the hydrogen peroxide (H2O2)-induced derangements of mechanical function and energy metabolism, and accumulation of intracellular Na+ were studied in isolated rat hearts. The intracellular concentration of Na+ ([Na+]i) in the myocardium was measured using a nuclear magnetic resonance technique. H2O2 (600 microM) increased the left ventricular end-diastolic pressure, decreased the tissue level of ATP, and increased the release of lactate dehydrogenase from the myocardium. These alterations induced by H2O2 were significantly attenuated by D-cis-diltiazem (15 microM) or L-cis-diltiazem (15 microM). H2O2 (1 mM) produced a marked increase in the myocardial [Na+]i, which was effectively inhibited by tetrodotoxin (3 microM), D-cis-diltiazem (15 microM) or L-cis-diltiazem (15 microM). These results suggest that both D-cis- and L-cis-diltiazem protect the myocardium against the H2O2-induced derangements in the isolated, perfused rat heart. The protective action of D-cis- and L-cis-diltiazem may be due to their ability to inhibit the H2O2-induced increase in [Na+]i, at least in part.
Xiao
C Y
CY
Department of Pharmacology, Asahikawa Medical College, Japan.
Hara
A
A
Hashizume
H
H
Tanaka
K
K
Abiko
Y
Y
D000818:Animals; D002021:Buffers; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D012996:Solutions; D013237:Stereoisomerism; D013779:Tetrodotoxin / Q000494:pharmacology
D002021:Buffers; D002121:Calcium Channel Blockers; D016166:Free Radical Scavengers; D016877:Oxidants; D012996:Solutions; D013779:Tetrodotoxin; D012964:Sodium; D006861:Hydrogen Peroxide; D004110:Diltiazem