Simvastatin restores endothelial NO-mediated vasorelaxation in large arteries after myocardial infarction

Kathryn Bates, Charles E. Ruggeroli, Steven Goldman, Mohamed A. Gaballa

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Congestive heart failure (CHF) after myocardial infarction is associated with diminished endothelial nitric oxide (NO)-mediated vasorelaxation. The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors have been shown to modulate vascular tone independent of the effects on lipid lowering. We hypothesized that simvastatin restores NO-dependent vasorelaxation with CHF. We found that incubation of the normal rat aorta with 0.1 mM simvastatin for 24 h enhanced ACh-mediated vasorelaxation (P < 0.05). Moreover, simvastatin increased (P < 0.05) endothelial NO synthase (eNOS) protein content by >200% (82.0 ± 14.0 vs. 21.6 ± 7.9% II/μg). In cultured endothelial cells, simvastatin (10 and 20 μM) increased eNOS levels by 114.7 ± 39.9 and 212.0 ± 75.0% II/μg protein, respectively (both P < 0.05; n = 8). In the rat coronary artery ligation model, oral gavage with 20 mg·kg -1·day -1 simvastatin for 3 wk decreased (P < 0.05) mean arterial pressure (121 ± 20 vs. 96.5 ± 10.8 mmHg) and left ventricular change in pressure with time (4,500 ± 700 vs. 4,091 ± 1,064 mmHg/s, n = 6). Simvastatin reduced (P < 0.05) basal vasoconstriction and improved ACh-mediated vasorelaxation in CHF arterial rings. Inhibition of NO generation by N G-nitro-L-arginine methyl ester (100 μM) abolished the ACh-induced vasorelaxation in all rats. In conclusion, chronic treatment of CHF with simvastatin restores endothelial NO-dependent dysfunction and upregulates eNOS protein content in arterial tissue.

Original languageEnglish (US)
Pages (from-to)H768-H775
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number2 52-2
StatePublished - Jul 30 2002

Keywords

  • 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors
  • Arterial relaxation
  • Congestive heart failure
  • Endothelial nitric oxide synthase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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