title: K(ATP) activation prevents progression of cardiac hypertrophy to failure induced by pressure overload via protecting endothelial function.
abstract: OBJECTIVE
  We investigated the effects of iptakalim, a new ATP-sensitive potassium channel (K(ATP)) opener providing endothelial protection, on the progression of cardiac hypertrophy to failure in a rat model of pressure overloading caused by abdominal aortic banding (AAB). Endothelial dysfunction is central to cardiac hypertrophy and failure induced by pressure overload. It would be useful to clarify whether iptakalim could prevent this.
  
  
  RESULTS
  The effects of pressure overload were assessed in male Sprague-Dawley rats 6 weeks after AAB using progression of cardiac hypertrophy to heart failure as the endpoint. The AAB-treated rats had significantly elevated blood pressure, systolic and diastolic cardiac dysfunction, evidence of left ventricular hypertrophy (LVH), and transition to heart failure. LVH was characterized by increases in the ratios of heart and left ventricular weights to body weight, increased myocyte cross-sectional areas, myocardial and perivascular fibrosis, and elevated cardiac hydroxyproline. These could be prevented by treatment with iptakalim at daily oral doses of 1, 3, and 9 mg/kg for 6 weeks. Progression to cardiac failure, demonstrated by increases in relative lung and right ventricular weights, cardiac function disorders and overexpression of atrial and B-type natriuretic peptide mRNA, could also be prevented. The downregulated nitric oxide signalling system was enhanced, whereas the upregulated endothelin signalling system was inhibited, resulting in normalization of the balance between these two systems.
  
  
  CONCLUSIONS
  Iptakalim protected the endothelium and prevented progression of cardiac hypertrophy to failure induced by a pressure overload.
authors.affiliation: Department of Cardiovascular Pharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.forename: Chao-Liang
authors.initials: CL
authors.lastname: Long
authors.forename: Ru-Huan
authors.initials: RH
authors.lastname: Wang
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005355:Fibrosis; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D006973:Hypertension / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D054086:KATP Channels / Q000819:agonists* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D019332:Endothelin-1; D054086:KATP Channels; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D011437:Propylamines; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D006909:Hydroxyproline