title: Iptakalim ameliorates monocrotaline-induced pulmonary arterial hypertension in rats.
abstract: OBJECTIVE
  We sought to investigate the experimental therapeutic effects and mechanisms of iptakalim, a new adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP)) opener, on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and right heart ventricle remodeling in rats.
  
  
  METHODS
  Rats were injected with a single dose (50 mg/kg, ip) of MCT and given iptakalim (1, 3, and 9 mg/kg·per d, orally [po]) or saline for 28 days. The hemodynamic and morphometric parameters were assessed. Tissue and plasma samples were collected for histological and molecular analysis.
  
  
  RESULTS
  Treatment with iptakalim at daily oral doses of 1, 3, and 9 mg/kg from the day of MCT injection attenuated the high right ventricle systolic pressure (RVSP) and the increased weight ratio of right ventricle (RV) to left ventricle (LV) plus septum (S) (RV/(LV+S)), decreased heart rate (HR) and decreased mean arterial pressure (MAP), inhibited the RV myocardial tissue cell apoptosis, and the RV myocardial cell B-type natriuretic peptide (BNP) protein expression. Iptakalim also decreased the serum levels of nitric oxide (NO), endothelin 1 (ET-1), BNP, and the levels of NO, ET-1, and tumor necrosis factor-alpha (TNF-α) in the lung tissue.
  
  
  CONCLUSIONS
  These results indicate that iptakalim prevents MCT-induced PAH and RV remodeling and its mechanisms are related to inhibiting the pathological increases in NO, ET-1, BNP, and TNF-α, and Iptakalim may be a promising candidate for the treatment of PAH.
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Junshan
authors.initials: J
authors.lastname: Li
authors.forename: Chaoliang
authors.initials: C
authors.lastname: Long
authors.forename: Wenyu
authors.initials: W
authors.lastname: Cui
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000037:antagonists & inhibitors; D065627:Familial Primary Pulmonary Hypertension; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy; D054086:KATP Channels / Q000187:drug effects*; D008168:Lung / Q000473:pathology; D008297:Male; D016686:Monocrotaline / Q000633:toxicity*; D020097:Natriuretic Peptide, Brain / Q000037:antagonists & inhibitors / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis; D011437:Propylamines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019332:Endothelin-1; D054086:KATP Channels; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D011437:Propylamines; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; D016686:Monocrotaline