title: Catalpol decreases peroxynitrite formation and consequently exerts cardioprotective effects against ischemia/reperfusion insult.
abstract: BACKGROUND
  Peroxynitrite (ONOO(-)) formation triggers oxidative/nitrative stress and contributes to exacerbated myocardial ischemia/reperfusion (MI/R) injury. Catalpol, an iridoid glycoside, abundantly found in the roots of Rehmannia glutinosa L. that is included in the family Phrymaceae in the order Lamiales, endemic to China, was found to have neuroprotective effects. However, the effect of catalpol on MI/R injury has not been identified.
  
  
  OBJECTIVE
  This study investigated whether catalpol attenuates oxidative/nitrative stress in acute MI/R.
  
  
  METHODS
  Adult male rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion and were treated with saline, catalpol (5 mg/kg, i.p., 5 min before reperfusion) or catalpol plus wortmannin (15 µg/kg intraperitoneally injected 15 min before reperfusion).
  
  
  RESULTS
  Pretreatment with catalpol significantly improved cardiac functions, reduced myocardial infarction, apoptosis and necrosis of cardiomyocytes after MI/R (all p < 0.05). Meanwhile, ONOO(-) formation was markedly reduced after catalpol treatment (3.01 ± 0.22 vs. 4.66 ± 0.53 pmol/mg protein in vehicle, p < 0.05). In addition, catalpol increased Akt and endothelial nitric oxide synthase phosphorylation, nitric oxide (NO) production, anti-oxidant capacity and reduced MI/R-induced inducible nitric oxide synthase expression and superoxide anion (·O(2)(-)) production in I/R hearts. PI3K inhibitor wortmannin not only blocked catalpol-induced Akt activation, but also attenuated all the beneficial effects of catalpol. Suppression of ONOO(-) formation by either catalpol or an ONOO(-) scavenger uric acid (5 mg/kg) reduced myocardial infarct size in MI/R rats.
  
  
  CONCLUSIONS
  In conclusion, catalpol affords cardioprotection against MI/R insult by attenuating ONOO(-) formation, which is attributable to increased physiological NO and decreased ·O(2)(-) production.
authors: Heart Center, First Hospital, Tsinghua University, Beijing, China.
authors: Chaolian
authors: C
authors: Huang
authors: Yongliang
authors: Y
authors: Cui
authors: Lele
authors: L
authors: Ji
authors: Wei
authors: W
authors: Zhang
authors: Rong
authors: R
authors: Li
authors: Lei
authors: L
authors: Ma
authors: Wenjuan
authors: W
authors: Xing
authors: Heping
authors: H
authors: Zhou
authors: Baoying
authors: B
authors: Chen
authors: Jun
authors: J
authors: Yu
authors: Haifeng
authors: H
authors: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004789:Enzyme Activation; D016166:Free Radical Scavengers / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D057888:Iridoid Glucosides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D016166:Free Radical Scavengers; D057888:Iridoid Glucosides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D030421:Peroxynitrous Acid; C078040:catalpol; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt