Effect of pravastatin on left ventricular mass by activation of myocardial KATP 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 ± 277μm 2 , 3372 ± 228μm 2 versus 4388 ± 163μm 2 in the vehicle group, both P 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.