title: Tolvaptan improves left ventricular dysfunction after myocardial infarction in rats.
abstract: BACKGROUND
  Arginine vasopressin, which promotes the reabsorption of renal water is increased in chronic heart failure. Here, we compared the effects of tolvaptan, a newly developed nonpeptide V(2) receptor antagonist, with those of furosemide, a loop diuretic, and a combination of these 2 agents in rats with left ventricular dysfunction after myocardial infarction (MI).
  
  
  RESULTS
  After 10 weeks of MI induction, the rats were separated them into the following 6 groups adjusted to the infarct size: a vehicle group, a group treated with 15 mg·kg(-1)·day(-1) of furosemide, 2 groups treated with 3 or 10 mg·kg(-1)·day(-1) of tolvaptan; and 2 groups treated with 15 mg·kg(-1)·day(-1) of furosemide plus 3 or 10 mg·kg(-1)·day(-1) tolvaptan. Each treatment agent was administered for 4 weeks, and all groups had similar blood pressure levels and infarct size. The tolvaptan-treated groups were found to have lower levels of left ventricular end-diastolic and systolic cardiac volumes than the vehicle group did. Furthermore, the improvement in the ejection fraction in the tolvaptan-treated groups was significantly greater than those in the vehicle group. ED-1 immunostaining and Sirius red staining revealed that tolvaptan significantly repressed MI-induced macrophage infiltration and interstitial fibrosis in the left ventricle, respectively. Tolvaptan attenuated the MI-induced mRNA expressions of atrial and brain natriuretic peptides, monocyte chemotactic protein-1, transforming growth factor-β1, arginine vasopressin V(1a) receptor, and endothelin-1 in the marginal infarct region.
  
  
  CONCLUSIONS
  Tolvaptan may improve cardiac dysfunction after MI, which is partially mediated by the suppression of V(1a) receptor, neurohumoral activation and inflammation.
authors.affiliation: Department of Internal Medicine and Cardiology, Osaka City University Medical School, Osaka, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Yasukatsu
authors.initials: Y
authors.lastname: Izumi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamashita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujiki
authors.forename: Mayuko
authors.initials: M
authors.lastname: Osada-Oka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shiota
authors.forename: Akihisa
authors.initials: A
authors.lastname: Hanatani
authors.forename: Kenei
authors.initials: K
authors.lastname: Shimada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwao
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshiyama
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005665:Furosemide / Q000494:pharmacology / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D051381:Rats; D017208:Rats, Wistar; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D000077602:Tolvaptan; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D049994:Sodium Potassium Chloride Symporter Inhibitors; D000077602:Tolvaptan; D005665:Furosemide