This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Greenberg, S. Articles by Keren, G. Search for Related Content PubMed Articles by Greenberg, S. Articles by Keren, G. Social Bookmarking                         What's this?

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

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

Gil Chemin

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

Itzhak Shapira

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

Jacob George

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

Yoram Wollman

Department of Nephrology, Tel-Aviv Medical Center, Israel

Shlomo Laniado

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

Gad Keren

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

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.

Key Words: captopril • L-arginine • ischemia-reperfusion • isolated heart.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 5, No. 4, 281-290 (2000)
DOI: 10.1054/JCPT.2000.18021


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?