Effect of pravastatin on left ventricular mass by activation of myocardial KATP channels in hypercholesterolemic rabbits

Tsung-Ming Lee, Mei Shu Lin, Tsai Fwu Chou, Chang Her Tsai, Nen Chung Chang

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Epidemiological studies showed that hypercholesterolemia was associated with a higher left ventricular mass. Myocardial ATP-sensitive potassium (K ATP) channels have been implicated in the development of cardiac hypertrophy. We investigated the effect of pravastatin on hypercholesterolemia- induced ventricular hypertrophy and whether the attenuated hypertrophic effect was via activation of myocardial KATP channels. In this study, we evaluated the hemodynamic, biochemical, and morphological responses to pravastatin in cholesterol-fed (1%) rabbits. Male New Zealand White rabbits were randomized to either vehicle, nicorandil (an agonist of KATP channels), pravastatin, glibenclamide (an antagonist of KATP channels), or a combination of nicorandil and glibenclamide or pravastatin and glibenclamide for 8 weeks. The left ventricular weight and left ventricular myocyte sizes increased 8 weeks after cholesterol-feeding in comparison to that in normocholesterolemic rabbits. Pravastatin administration significantly decreased the left ventricular weight by 12% and cardiomyocyte cell areas by 30%. Hyperlipidemic rabbits in the nicorandil- and pravastatin-treated groups significantly attenuated cardiomyocyte hypertrophy, as compared with the vehicle-treated group (3162 ± 277 μm2, 3372 ± 228 μm2 versus 4388 ± 163 μm2 in the vehicle group, both P <0.0001, respectively). Nicorandil-induced effects were abolished by administering glibenclamide. Similarly, pravastatin-induced beneficial effects were reversed by the addition of glibenclamide, implicating KATP channels as the relevant target. The results of the present study suggest a pathogenetic role of KATP channels in hypercholesterolemia-induced ventricular hypertrophy. The antihypertropic effects of pravastatin may be related to activation of KATP channels, and result in an amelioration of cardiomyocyte hypertrophy development by an atherogenic diet.

Original languageEnglish
Pages (from-to)273-278
Number of pages6
JournalAtherosclerosis
Volume176
Issue number2
DOIs
Publication statusPublished - Oct 2004

Fingerprint

Pravastatin
KATP Channels
Glyburide
Nicorandil
Rabbits
Hypertrophy
Hypercholesterolemia
Cardiac Myocytes
Cholesterol
Atherogenic Diet
Weights and Measures
Cardiomegaly
Muscle Cells
Epidemiologic Studies
Adenosine Triphosphate
Hemodynamics

Keywords

  • ATP-sensitive potassium channels
  • Hyperlipidemia
  • Pravastatin
  • Ventricular mass

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effect of pravastatin on left ventricular mass by activation of myocardial KATP channels in hypercholesterolemic rabbits. / Lee, Tsung-Ming; Lin, Mei Shu; Chou, Tsai Fwu; Tsai, Chang Her; Chang, Nen Chung.

In: Atherosclerosis, Vol. 176, No. 2, 10.2004, p. 273-278.

Research output: Contribution to journalArticle

Lee, Tsung-Ming ; Lin, Mei Shu ; Chou, Tsai Fwu ; Tsai, Chang Her ; Chang, Nen Chung. / Effect of pravastatin on left ventricular mass by activation of myocardial KATP channels in hypercholesterolemic rabbits. In: Atherosclerosis. 2004 ; Vol. 176, No. 2. pp. 273-278.
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AB - Epidemiological studies showed that hypercholesterolemia was associated with a higher left ventricular mass. Myocardial ATP-sensitive potassium (K ATP) channels have been implicated in the development of cardiac hypertrophy. We investigated the effect of pravastatin on hypercholesterolemia- induced ventricular hypertrophy and whether the attenuated hypertrophic effect was via activation of myocardial KATP channels. In this study, we evaluated the hemodynamic, biochemical, and morphological responses to pravastatin in cholesterol-fed (1%) rabbits. Male New Zealand White rabbits were randomized to either vehicle, nicorandil (an agonist of KATP channels), pravastatin, glibenclamide (an antagonist of KATP channels), or a combination of nicorandil and glibenclamide or pravastatin and glibenclamide for 8 weeks. The left ventricular weight and left ventricular myocyte sizes increased 8 weeks after cholesterol-feeding in comparison to that in normocholesterolemic rabbits. Pravastatin administration significantly decreased the left ventricular weight by 12% and cardiomyocyte cell areas by 30%. Hyperlipidemic rabbits in the nicorandil- and pravastatin-treated groups significantly attenuated cardiomyocyte hypertrophy, as compared with the vehicle-treated group (3162 ± 277 μm2, 3372 ± 228 μm2 versus 4388 ± 163 μm2 in the vehicle group, both P <0.0001, respectively). Nicorandil-induced effects were abolished by administering glibenclamide. Similarly, pravastatin-induced beneficial effects were reversed by the addition of glibenclamide, implicating KATP channels as the relevant target. The results of the present study suggest a pathogenetic role of KATP channels in hypercholesterolemia-induced ventricular hypertrophy. The antihypertropic effects of pravastatin may be related to activation of KATP channels, and result in an amelioration of cardiomyocyte hypertrophy development by an atherogenic diet.

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