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

Abstract

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.

• Authors: Tsung-Ming Lee, Mei-Shu Lin, Chang-Her Tsai, Nen-Chung Chang
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 291 Issue 6 Pg. H2705-13 (Dec 2006) ISSN: 0363-6135 [Print] United States
• PMID: 16798829 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Arrhythmia Agents
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Potassium Channels
• Vasodilator Agents
• mitochondrial K(ATP) channel
• Nicorandil
• Hydralazine
• Atrial Natriuretic Factor
• Pravastatin
• Glyburide

Topics

• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Atrial Natriuretic Factor (genetics, metabolism)
• Echocardiography
• Gene Expression Regulation (drug effects)
• Glyburide (pharmacology)
• Heart Ventricles (drug effects, pathology)
• Hydralazine (pharmacology)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Hypertension, Renal (complications, pathology)
• Hypertrophy, Left Ventricular (physiopathology, prevention & control)
• Male
• Nicorandil (pharmacology)
• Potassium Channels (drug effects, physiology)
• Pravastatin (pharmacology)
• Rats
• Rats, Wistar
• Vasodilator Agents (pharmacology)