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 μm 2, 3372 ± 228 μm 2 versus 4388 ± 163 μm 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.
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