Effect of pravastatin on left ventricular mass by activation of myocardial K ATP channels in hypercholesterolemic rabbits.

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 K(ATP) 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 K(ATP) channels), pravastatin, glibenclamide (an antagonist of K(ATP) 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 microm(2), 3372 +/- 228 microm(2) versus 4388 +/- 163 microm(2) 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 K(ATP) channels as the relevant target. The results of the present study suggest a pathogenetic role of K(ATP) channels in hypercholesterolemia-induced ventricular hypertrophy. The antihypertropic effects of pravastatin may be related to activation of K(ATP) channels, and result in an amelioration of cardiomyocyte hypertrophy development by an atherogenic diet.

• Authors: Tsung-Ming Lee, Mei-Shu Lin, Tsai-Fwu Chou, Chang-Her Tsai, Nen-Chung Chang
• Journal: Atherosclerosis (Atherosclerosis) Vol. 176 Issue 2 Pg. 273-8 (Oct 2004) ISSN: 0021-9150 [Print] Ireland
• PMID: 15380449 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticholesteremic Agents
• Potassium Channels
• Adenosine Triphosphate
• Pravastatin

Topics

• Adenosine Triphosphate
• Animals
• Anticholesteremic Agents (pharmacology)
• Disease Models, Animal
• Heart (drug effects, physiology)
• Hypercholesterolemia (drug therapy, physiopathology, veterinary)
• Hypertrophy, Left Ventricular (drug therapy, physiopathology, veterinary)
• Male
• Potassium Channels (drug effects, physiology)
• Pravastatin (pharmacology)
• Rabbits