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Effect of pravastatin on left ventricular mass in the two-kidney, one-clip hypertensive rats

¹Cardiology Section, Department of Medicine, Taipei Medical University and Chi-Mei Medical Center, Tainan; ²Department of Pharmacy, National Taiwan University Hospital, Taipei; ³Cardiology Section, Department of Surgery, E-DA Hospital and I-Shou University, Kaohsiung; and ⁴Cardiology Section, Department of Medicine, Taipei Medical University and Hospital, Taipei, Taiwan

Submitted 2 March 2006 ; accepted in final form 6 June 2006

We have demonstrated that myocardial ATP-sensitive potassium (K_ATP) channels are implicated in the development of cardiac hypertrophy in hyperlipidemic rabbits. We investigated the effect of pravastatin on development of ventricular hypertrophy in male normolipidemic Wistar rats with two-kidney, one-clip (2K1C) hypertension and whether the attenuated hypertrophic effect was via activation of K_ATP channels. Twenty-four hours after the left renal artery was clipped, rats were treated with one of the following therapies for 8 wk: vehicle, nicorandil (an agonist of K_ATP channels), pravastatin, glibenclamide (an antagonist of K_ATP channels), hydralazine, nicorandil plus glibenclamide, or pravastatin plus glibenclamide. Systolic blood pressure, relative left ventricular (LV) weight, and cardiomyocyte sizes significantly increased in vehicle-treated 2K1C rats compared with those in sham-operated rats. Treatment with either nicorandil or pravastatin significantly attenuated LV hypertrophy/body weight compared with the vehicle, which was further confirmed by downregulation of LV atrial natriuretic peptide mRNA. 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. A dissociation between the effects of blood pressure and cardiac structure was noted because pravastatin and hydralazine reduced arterial pressure similarly. These results suggest a crucial role of cardiac K_ATP channel system in the development of ventricular hypertrophy in the 2K1C hypertensive rats. Pravastatin is endowed with cardiac antihypertrophic properties probably through activation of K_ATP channels, independent of lipid and hemodynamic changes.

hypertension; ion channels; statins

This article has been cited by other articles:

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