title: Captopril and L-arginine have a synergistic cardioprotective effect in ischemic-reperfusion injury in the isolated rat heart.
abstract: OBJECTIVE
  The present study was designed to evaluate the possible effect of the combined administration of both captopril (Cap) and L-arginine (L-a) in the isolated ischemic rat heart model.
  
  
  BACKGROUND
  Recent studies suggest that L-arginine and angiotensin-converting enzyme (ACE) inhibitors possess independent cardioprotective effects in ischemic hearts. The pharmacological effect of the combination of both drugs has not yet been investigated in the ischemic myocardium.
  
  
  METHODS
  Using the modified Langendorf model, rats were perfused with either Cap 360 micromol/L (n = 6) or (L-a) 3mmol/L (n = 6), both captopril and L-arginine (Cap+L-a) (n = 8), or saline control (Con) (n = 8). The study design included 30 minutes of perfusion, 30 minutes of global ischemia, and 30 minutes of reperfusion thereafter.
  
  
  RESULTS
  Hearts treated with both Cap+L-a demonstrated an improved performance in all parameters. After 10 minutes of reperfusion, the P(max) in the Cap+L-a group was 98 +/- 8 mmHg (P <.001), 59 +/- 14 mmHg in the Cap group (P <.02), and 44.3 +/- 10 mmHg in the L-a group (P = NS), compared with only 42 +/- 8 mmHg in the control. After 10 minutes of reperfusion the dP/dt(min) was: in the Cap+L-a group: -1,650 +/- 223 mmHg/s (P <. 006); in the Cap group: -1,051 +/- 302 mmHg/s (P <.03); in the L-a group: -870 +/- 131 mmHg/s (P = NS), compared with only -487 +/- 131 mmHg/s in the control. Coronary flow was significantly increased in all 3 groups: Cap+L-a group: 22.3 +/- 1.5 mL/min (P <.001); Cap group: 18 +/- 1.6 mL/min (P <.01); L-a group: 19.8 +/- 0.9 mL/min (P <.02), compared with 12.6 +/- 0.9 mL/min in the Con group. Total NO level was significantly increased in the Cap+L-a group: 13.4 +/- 2 micromol (P <.03) vs. 6.1 +/- 1 micromol for the L-a group. NO levels of both the Cap group and the Con group were beneath detectable values.
  
  
  CONCLUSIONS
  Combined administration of captopril and L-arginine has a synergistic, protective effect on heart function and coronary flow that may be mediated by enhanced NO production.
authors.affiliation: Cardiovascular Research Laboratory, Cardiology Department, Tel-Aviv Medical Center, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Greenberg
authors.forename: G
authors.initials: G
authors.lastname: Chernin
authors.forename: I
authors.initials: I
authors.lastname: Shapira
authors.forename: J
authors.initials: J
authors.lastname: George
authors.forename: Y
authors.initials: Y
authors.lastname: Wollman
authors.forename: S
authors.initials: S
authors.lastname: Laniado
authors.forename: G
authors.initials: G
authors.lastname: Keren
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D046508:Culture Techniques; D004359:Drug Therapy, Combination; D006439:Hemodynamics; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D002216:Captopril