Atorvastatin worsens left ventricular diastolic dysfunction and endothelial dysfunction of epicardial coronary arteries in normocholesterolemic porcine with left ventricular hypertrophy

Jessica Forcillo, Simon Maltais, Marie Claude Aubin, Yan Fen Shi, Michel Carrier, Jean Claude Tardif, Louis P. Perrault

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Statins have pleiotropic effects that can reverse endothelial dysfunction and prevent the development of left ventricular hypertrophy (LVH). The goal of this study was to assess the effect of treatment with atorvastatin on the endothelial dysfunction of epicardial coronary arteries and the development of LVH in a porcine model. LVH was induced through 2 months of aortic banding (AB) of the ascending aorta. Experimental groups were (1) sham untreated: without AB, (2) LVH untreated: with AB, and (3,4) LVH treated: with AB treated with 40 and 80 mg of atorvastatin, respectively, for 60 days, and (5) sham treated: without AB treated with 80 mg of atorvastatin for 60 days. Vascular reactivity studies were performed in organ chambers experiments. NO bioavailability was assessed using cyclic guanosine monophosphate quantification. Oxidative stress levels were measured by quantifying angiotensin II) and nitrite/nitrate levels. LVH and LV diastolic function were evaluated using echocardiography. Atorvastatin decreased endothelium-dependent relaxations and cyclic guanosine monophosphate levels in all treated animals. Angiotensin II levels were increased, whereas nitrite levels were similar among groups (P > 0.05). LV diastolic dysfunction and LVH were significantly greater in all treated animals (P < 0.01). High-density lipoprotein levels and low-density lipoprotein levels were significantly decreased in animals receiving atorvastatin (P < 0.05). In this swine model of LVH, atorvastatin did not prevent LVH development or coronary endothelial dysfunction and resulted in worsening of the LV diastolic dysfunction.

Original languageEnglish (US)
Pages (from-to)295-306
Number of pages12
JournalJournal of Cardiovascular Pharmacology
Volume58
Issue number3
DOIs
StatePublished - Sep 1 2011

Keywords

  • coronary arteries
  • endothelial dysfunction
  • left ventricular hypertrophy
  • oxidative stress
  • statins

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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