Lindera strychnifolia is protective against post-ischemic myocardial dysfunction through scavenging hydroxyl radicals and opening the mitochondrial KATP channels in isolated rat hearts.
Lindera strychnifolia (tendai-uyaku), a medicinal plant, has long been used for the treatment of cardiac, renal and rheumatic diseases in Japan. We aim to clarify (1) whether L. strychnifolia is protective against post-ischemic myocardial dysfunction, and (2) whether its effect is related to scavenging hydroxyl radicals and opening the mitochondrial KATP channels in isolated rat hearts. Male Sprague-Dawley rats were orally given 1 ml/day of L. strychnifolia, which was extracted from 0.75 and 1.5 g/kg of roots of L. strychnifolia for 4 days. The rat hearts were excised and perfused on a Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O2 and 5% CO2. The hearts were paced at 320 beats/min except during ischemia. Left ventricular developed pressure (LVDP, mmHg), +/- dP/dt (mmHg/sec) and coronary flow (ml/min) were continuously monitored. All hearts were perfused for a total of 120 minutes consisting of a 30-minute pre-ischemic period followed by 30 minutes of global ischemia and 60 minutes of reperfusion with or without 5-HD, a mitochondrial KATP channel blocker. The levels of lactate, LDH and 2,5-DHBA, an indicator of hydroxyl radicals, in the perfusate during reperfusion period were also measured. Treatment with L. strychnifolia significantly improved LVDP and +/- dP/dt without altering coronary flow during reperfusion. The 100 microM of 5-HD in Krebs-Henseleit solution was perfused during the 10 minutes of pre-ischemic periods. Pretreatment with 5-HD abolished the improvement of LVDP and +/- dP/dt by L. strychnifolia. L. strychnifolia significantly attenuated the levels of lactate, LDH and 2,5-DHBA during reperfusion, and which were restored by pretreatment with 5-HD. In conclusion, L. strychnifolia is protective against post-ischemic left ventricular dysfunction through scavenging hydroxyl radicals and opening the KATP channels in the isolated rat heart.
Wang
Ningyuan
N
Second Department of Internal Medicine, Gifu University School of Medicine 40 Tsukasa-Machi, Gifu, 500-8705, Japan.
Minatoguchi
Shinya
S
Arai
Masazumi
M
Uno
Yoshihiro
Y
Hashimoto
Kazuaki
K
Xue-Hai
Chen
C
Fukuda
Kazunori
K
Akao
Seigo
S
Takemura
Genzou
G
Fujiwara
Hisayoshi
H
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005841:Gentisates / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D017665:Hydroxyl Radical / Q000378:metabolism*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D027443:Lindera; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D028321:Plant Preparations / Q000494:pharmacology* / Q000627:therapeutic use; D015221:Potassium Channels; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
D005841:Gentisates; D008565:Membrane Proteins; D028321:Plant Preparations; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D017665:Hydroxyl Radical; D007770:L-Lactate Dehydrogenase; C010925:2,5-dihydroxybenzoic acid