Captopril and L-Arginine Have a Synergistic Cardioprotective Effect in Ischemic-Reperfusion Injury in the Isolated Rat Heart

Abstract

Objectives: 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 μmol/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 mmHb/s (P < .03); in the L-a group: -870 ± 131 mmHg/s (P = NS), compared with only -487 ± 131 mmHb/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 μmol ( P < .03) vs. 6.1 ± 1 μmol for the L-a group. NO levels of both the Cap group and the Con group were beneath detectable values.

Conclusion: 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.

Keywords

captopril L-arginine ischemia-reperfusion isolated heart.

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