title: Long-term stimulation of adenosine A2b receptors begun after myocardial infarction prevents cardiac remodeling in rats.
abstract: BACKGROUND
  Adenosine inhibits proliferation of cardiac fibroblasts and hypertrophy of cardiomyocytes, both of which may play crucial roles in cardiac remodeling. In the present study, we investigated whether chronic stimulation of adenosine receptors begun after myocardial infarction (MI) prevents cardiac remodeling.
  
  
  RESULTS
  MI was produced in Wistar rats by permanent ligation of the left anterior descending coronary artery. One week after the onset of MI, animals were randomized into 8 groups: vehicle, dipyridamole (DIP; the adenosine uptake inhibitor, 50 mg/kg), 2-chroloadenosine (CADO; the stable analogue of adenosine, 2 mg/kg), and CADO in the presence of the nonselective adenosine receptor antagonist 8-sulfophenyltheophylline (8-SPT) or the selective antagonist for adenosine A1, A2a, A2b, or A3 receptor. Three weeks after treatment, hemodynamic and echocardiographic parameters in the DIP and CADO groups were significantly improved compared with the vehicle group. These hemodynamic and echocardiographic improvements were blunted by either 8-SPT or the selective adenosine A2b antagonist MRS1754 but not by the selective antagonists for other subtypes of adenosine receptors. The collagen volume fraction was smaller, and gene expression of the molecules associated with cardiac remodeling such as matrix metalloproteinase in noninfarcted areas was reduced in the DIP and CADO groups compared with the vehicle group, both of which were attenuated by either 8-SPT or MRS1754.
  
  
  CONCLUSIONS
  Long-term stimulation of adenosine A2b receptors begun after MI attenuates cardiac fibrosis in the noninfarcted myocardium and improves cardiac function. Drugs that stimulate adenosine A2b receptors or increase adenosine levels are new candidates for preventing cardiac remodeling after MI.
authors.affiliation: Department of Bioregulatory Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Wakeno
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Osamu
authors.initials: O
authors.lastname: Seguchi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Okazaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Tsukamoto
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Okada
authors.forename: Akio
authors.initials: A
authors.lastname: Hirata
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Jiyoong
authors.initials: J
authors.lastname: Kim
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komamura
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.forename: Naoki
authors.initials: N
authors.lastname: Mochizuki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D015762:2-Chloroadenosine / Q000494:pharmacology / Q000627:therapeutic use; D000081:Acetamides / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D006332:Cardiomegaly / Q000473:pathology; D003094:Collagen / Q000032:analysis; D005355:Fibrosis; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000081:Acetamides; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; C423842:N-(4-cyanophenyl)-2-(4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)-phenoxy)acetamide; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines; D012333:RNA, Messenger; D015762:2-Chloroadenosine; C031433:8-(4-sulfophenyl)theophylline; D003094:Collagen; D013806:Theophylline; D020782:Matrix Metalloproteinases