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J Cardiovasc Pharmacol Ther. 2000 Oct;5(4):281-90.

Captopril and L-arginine have a synergistic cardioprotective effect in ischemic-reperfusion injury in the isolated rat heart.

Author information

1
Cardiovascular Research Laboratory, Cardiology Department, Tel-Aviv Medical Center, Israel.

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 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.

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.

PMID:
11150398
DOI:
10.1054/JCPT.2000.18021
[Indexed for MEDLINE]

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