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

Tsung-Ming Lee, Mei S. Lin, Chang H. Tsai, Nen Chung Chang

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 KATP 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 KATP 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 KATP channel system in the development of ventricular hypertrophy in the 2K1C hypertensive rats. Pravastatin is endowed with cardiac antihypertrophic properties probably through activation of KATP channels, independent of lipid and hemodynamic changes.

Original languageEnglish
Pages (from-to)H2705-H2713
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number6
DOIs
Publication statusPublished - 2006

Fingerprint

Pravastatin
Surgical Instruments
KATP Channels
Glyburide
Nicorandil
Kidney
Hydralazine
Adenosine Triphosphate
Blood Pressure
Hypertrophy
Cardiomegaly
Left Ventricular Hypertrophy
Atrial Natriuretic Factor
Renal Artery
Cardiac Myocytes
Wistar Rats
Arterial Pressure
Down-Regulation
Hemodynamics
Body Weight

Keywords

  • Hypertension
  • Ion channels
  • Statins

ASJC Scopus subject areas

  • Physiology

Cite this

Effect of pravastatin on left ventricular mass in the two-kidney, one-clip hypertensive rats. / Lee, Tsung-Ming; Lin, Mei S.; Tsai, Chang H.; Chang, Nen Chung.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 291, No. 6, 2006, p. H2705-H2713.

Research output: Contribution to journalArticle

@article{dd671395f49b45a4958ea637acaeb863,
title = "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 KATP 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 KATP 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 KATP channel system in the development of ventricular hypertrophy in the 2K1C hypertensive rats. Pravastatin is endowed with cardiac antihypertrophic properties probably through activation of KATP channels, independent of lipid and hemodynamic changes.",
keywords = "Hypertension, Ion channels, Statins",
author = "Tsung-Ming Lee and Lin, {Mei S.} and Tsai, {Chang H.} and Chang, {Nen Chung}",
year = "2006",
doi = "10.1152/ajpheart.00224.2006",
language = "English",
volume = "291",
pages = "H2705--H2713",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "6",

}

TY - JOUR

T1 - Effect of pravastatin on left ventricular mass in the two-kidney, one-clip hypertensive rats

AU - Lee, Tsung-Ming

AU - Lin, Mei S.

AU - Tsai, Chang H.

AU - Chang, Nen Chung

PY - 2006

Y1 - 2006

N2 - 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 KATP 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 KATP 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 KATP channel system in the development of ventricular hypertrophy in the 2K1C hypertensive rats. Pravastatin is endowed with cardiac antihypertrophic properties probably through activation of KATP channels, independent of lipid and hemodynamic changes.

AB - 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 KATP 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 KATP 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 KATP channel system in the development of ventricular hypertrophy in the 2K1C hypertensive rats. Pravastatin is endowed with cardiac antihypertrophic properties probably through activation of KATP channels, independent of lipid and hemodynamic changes.

KW - Hypertension

KW - Ion channels

KW - Statins

UR - http://www.scopus.com/inward/record.url?scp=33845439989&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845439989&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00224.2006

DO - 10.1152/ajpheart.00224.2006

M3 - Article

C2 - 16798829

AN - SCOPUS:33845439989

VL - 291

SP - H2705-H2713

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 6

ER -