title: Natakalim improves post-infarction left ventricular remodeling by restoring the coordinated balance between endothelial function and cardiac hypertrophy.
abstract: Endothelial dysfunction can lead to congestive heart failure and the activation of endothelial ATP-sensitive potassium (K(ATP)) channels may contribute to endothelial protection. Therefore, the present study was carried out to investigate the hypothesis that natakalim, a novel K(ATP) channel opener, ameliorates post-infarction left ventricular remodeling and failure by correcting endothelial dysfunction. The effects of myocardial infarction were assessed 8 weeks following left anterior descending coronary artery occlusion in male Wistar rats. Depressed blood pressure, cardiac dysfunction, evidence of left ventricular remodeling and congestive heart failure were observed in the rats with myocardial infarction. Treatment with natakalim at daily oral doses of 1, 3 or 9 mg/kg/day for 8 weeks prevented these changes. Natakalim also prevented the progression to cardiac failure, which was demonstrated by the increase in right ventricular weight/body weight (RVW/BW) and relative lung weight, signs of cardiac dysfunction, as well as the overexpression of atrial and brain natriuretic peptide mRNAs. Our results also demonstrated that natakalim enhanced the downregulation of endothelium-derived nitric oxide, attenuated the upregulation of inducible nitric oxide synthase-derived nitric oxide (NO), inhibited the upregulated endothelin system and corrected the imbalance between prostacyclin and thromboxane A(2). Overall, our findings suggest that natakalim prevents post-infarction hypertrophy and cardiac failure by restoring the coordinated balance between endothelial function and cardiac hypertrophy.
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Zhou
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Ming-Li
authors.initials: ML
authors.lastname: Zhong
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: Cardiovascular Drug Research Center, Thadweik Academy of Medicine, Beijing 100039, P.R. China.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Cui
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Chao-Liang
authors.initials: CL
authors.lastname: Long
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D011464:Epoprostenol / Q000097:blood; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006909:Hydroxyproline / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000097:blood; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000498:Allyl Compounds; D016232:Endothelins; D011437:Propylamines; C556401:natakalim; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; D013928:Thromboxane A2; D011464:Epoprostenol; D006909:Hydroxyproline