Asymmetric dimethylarginine (ADMA) induces vascular endothelium impairment and aggravates post-ischemic ventricular dysfunction in rats

Vito De Gennaro Colonna, Sara Bonomo, Paolo Ferrario, Mauro Bianchi, Marco Berti, Marco Guazzi, Barbara Manfredi, Eugenio E. Muller, Ferruccio Berti, Giuseppe Rossoni

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Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) inhibitor recognized as an independent risk factor for endothelial dysfunction and coronary heart diseases. This study investigated whether ADMA (10 mg/kg day for 14 days) affected endothelial function and aggravated post-ischemic ventricular dysfunction in the perfused rat heart. Systolic blood pressure and heart rate, plasma levels of ADMA and nitrite/nitrate were measured in vehicle- and ADMA-treated rats. Perfused hearts were submitted to global ischemia-reperfusion and vascular endothelial dysfunction was examined with angiotensin II in coronary vessels and aortic rings. Endothelial NO synthase (eNOS) and angiotensin-converting enzyme (ACE) mRNA expression in aortic and cardiac tissues were measured. ADMA-treated rats had higher systolic blood pressure (1.3-fold, P <0.01) and slower heart rate (16%, P <0.05) than controls. Plasma ADMA rose (1.9-fold, P <0.01) and nitrite/nitrate concentration decreased 59% (P <0.001). Ventricular contraction (stiffness) increased significantly, with worsening of post-ischemic ventricular dysfunction. In preparations from ADMA-treated rats the coronary vasculature's response to angiotensin II was almost doubled (P <0.01) and the maximal vasorelaxant effect of acetylcholine in aortic rings was significantly lower than in preparations from vehicle-treated rats. In cardiac and aortic tissues eNOS mRNA and ACE mRNA levels were similar in controls and ADMA-treated rats. The increased plasma levels of ADMA presumably cause endothelial dysfunction because of a deficiency in NO production, which also appears involved in the aggravation of myocardial ischemia-reperfusion injury.

Original languageEnglish
Pages (from-to)178-185
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number2-3
Publication statusPublished - Feb 28 2007


  • (Rat)
  • Asymmetric dimethylarginine
  • Endothelial dysfunction
  • Myocardial ischemia-reperfusion

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology


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