The protective effect of EGb 761 in isolated ischemic/reperfused rat hearts: a link between cardiac function and nitric oxide production.
This study was conducted to evaluate the effect of Ginkgo biloba extract (EGb 761) on the nitric oxide (NO) production in relation to the recovery of postischemic cardiac function in isolated working rat hearts. Rats were orally treated with various doses (25, 50, 75, and 100 mg/kg/day) of EGb 761 for 10 days. Hearts were isolated in "working mode" and subjected to 30-min ischemia followed by 120 min of reperfusion. EGb 761 inhibited NO production measured by electron spin-resonance spectroscopy (ESR), and improved the recovery of postischemic cardiac function (coronary flow, aortic flow, left ventricular developed pressure and its first derivative) in the ischemic/reperfused myocardium. Thus in rats treated with 25, 50, 75, and 100 mg/kg/day of EGb 761 and in hearts subjected to 30-min ischemia followed by 120 min of reperfusion, aortic flow was increased from its postischemic drug-free control value of 8.0+/-0.4 to 8.6+/-0.4 ml/min (NS), 17.3+/-0.9 ml/min (p<0.05), 21.5+/-1.1 ml/min (p<0.05), and 23.6+/-1.2 ml/min, respectively. The same recovery in postischemic coronary flow, left ventricular developed pressure, and its first derivative also was observed. In the initial phase of reperfusion, NO production measured by ESR was reduced by 85% in the 75 mg/ kg/day of EGb 761-treated group in comparison with the drug-free ischemic/reperfused hearts. Inducible NO synthase (iNOS) messenger RNA (mRNA) measured by reverse transcription-polymerase chain reaction (RT-PCR) also was reduced by 41 and 58% in the groups treated with 75 and 100 mg/kg/day of EGb 761, respectively. Our findings show that EGb 761 directly acts as an NO scavenger and concomitantly inhibits the expression of iNOS mRNA. Thus, EGb 761 may act as a potent inhibitor of NO production under the condition of ischemia/reperfusion, improving the recovery of postischemic cardiac function.
Varga
E
E
Department of Pharmacology, School of Medicine, Debrecen, Hungary.
Bodi
A
A
Ferdinandy
P
P
Droy-Lefaix
M T
MT
Blasig
I E
IE
Tosaki
A
A
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D005419:Flavonoids / Q000627:therapeutic use*; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D020441:Ginkgo biloba; D006334:Heart Function Tests; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts / Q000627:therapeutic use; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000096983:Ginkgo Extract
D005419:Flavonoids; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts; D012333:RNA, Messenger; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C496318:Nos2 protein, rat