Long-term administration of nifedipine attenuates cardiac remodeling and diastolic heart failure in hypertensive rats

Takashi Yamada, Kohzo Nagata, Xian Wu Cheng, Koji Obata, Masako Saka, Masaaki Miyachi, Keiko Naruse, Takao Nishizawa, Akiko Noda, Hideo Izawa, Masafumi Kuzuya, Kenji Okumura, Toyoaki Murohara, Mitsuhiro Yokota

Research output: Contribution to journalArticle

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Abstract

The Ca2+ channel blocker nifedipine has been reported to reduce the rate of new overt heart failure. We investigated the effects of nifedipine on left ventricular remodeling, oxidative stress, and gene expression in the failing heart of Dahl salt-sensitive (DS) rats. DS rats fed a high-salt diet from 7 weeks of age were treated with a non-antihypertensive (1 mg/kg per day, Nif-L) or mild-antihypertensive dose of nifedipine (3 mg/kg per day, Nif-H) or with vehicle (Vehicle) from 12 to 19 weeks. Marked left ventricular hypertrophy and fibrosis were apparent and the ratio of collagen type I to type III mRNA levels and the activity of matrix metalloproteinase (MMP)-2 and its mRNA expression in the myocardium were increased in Vehicle at 19 weeks in comparison with Control. Load-induced left ventricular hypertrophy was reduced in Nif-H, but not in Nif-L, relative to that in Vehicle. Treatment with either dose of nifedipine reduced the extent of fibrosis, the collagen type I to type III mRNA ratio, and MMP-2 activity and its mRNA expression compared with those in Vehicle. The decrease in the ratio of reduced to oxidized glutathione and the increase in NADPH oxidase activity apparent in the left ventricle of Vehicle were also inhibited by nifedipine at both doses. Nifedipine thus inhibited the development of left ventricular fibrosis and diastolic heart failure in DS rats, independently of its antihypertensive effect. The overall protective action of nifedipine is likely attributable to its antioxidant effect as well as to its antihypertensive action.

Original languageEnglish
Pages (from-to)163-170
Number of pages8
JournalEuropean Journal of Pharmacology
Volume615
Issue number1-3
DOIs
Publication statusPublished - 01-08-2009
Externally publishedYes

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Diastolic Heart Failure
Nifedipine
Inbred Dahl Rats
Antihypertensive Agents
Messenger RNA
Fibrosis
Matrix Metalloproteinase 2
Left Ventricular Hypertrophy
Collagen Type I
Ventricular Remodeling
Glutathione Disulfide
NADPH Oxidase
Heart Ventricles
Myocardium
Oxidative Stress
Heart Failure
Salts
Antioxidants
Diet
Gene Expression

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Yamada, Takashi ; Nagata, Kohzo ; Cheng, Xian Wu ; Obata, Koji ; Saka, Masako ; Miyachi, Masaaki ; Naruse, Keiko ; Nishizawa, Takao ; Noda, Akiko ; Izawa, Hideo ; Kuzuya, Masafumi ; Okumura, Kenji ; Murohara, Toyoaki ; Yokota, Mitsuhiro. / Long-term administration of nifedipine attenuates cardiac remodeling and diastolic heart failure in hypertensive rats. In: European Journal of Pharmacology. 2009 ; Vol. 615, No. 1-3. pp. 163-170.
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abstract = "The Ca2+ channel blocker nifedipine has been reported to reduce the rate of new overt heart failure. We investigated the effects of nifedipine on left ventricular remodeling, oxidative stress, and gene expression in the failing heart of Dahl salt-sensitive (DS) rats. DS rats fed a high-salt diet from 7 weeks of age were treated with a non-antihypertensive (1 mg/kg per day, Nif-L) or mild-antihypertensive dose of nifedipine (3 mg/kg per day, Nif-H) or with vehicle (Vehicle) from 12 to 19 weeks. Marked left ventricular hypertrophy and fibrosis were apparent and the ratio of collagen type I to type III mRNA levels and the activity of matrix metalloproteinase (MMP)-2 and its mRNA expression in the myocardium were increased in Vehicle at 19 weeks in comparison with Control. Load-induced left ventricular hypertrophy was reduced in Nif-H, but not in Nif-L, relative to that in Vehicle. Treatment with either dose of nifedipine reduced the extent of fibrosis, the collagen type I to type III mRNA ratio, and MMP-2 activity and its mRNA expression compared with those in Vehicle. The decrease in the ratio of reduced to oxidized glutathione and the increase in NADPH oxidase activity apparent in the left ventricle of Vehicle were also inhibited by nifedipine at both doses. Nifedipine thus inhibited the development of left ventricular fibrosis and diastolic heart failure in DS rats, independently of its antihypertensive effect. The overall protective action of nifedipine is likely attributable to its antioxidant effect as well as to its antihypertensive action.",
author = "Takashi Yamada and Kohzo Nagata and Cheng, {Xian Wu} and Koji Obata and Masako Saka and Masaaki Miyachi and Keiko Naruse and Takao Nishizawa and Akiko Noda and Hideo Izawa and Masafumi Kuzuya and Kenji Okumura and Toyoaki Murohara and Mitsuhiro Yokota",
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Yamada, T, Nagata, K, Cheng, XW, Obata, K, Saka, M, Miyachi, M, Naruse, K, Nishizawa, T, Noda, A, Izawa, H, Kuzuya, M, Okumura, K, Murohara, T & Yokota, M 2009, 'Long-term administration of nifedipine attenuates cardiac remodeling and diastolic heart failure in hypertensive rats', European Journal of Pharmacology, vol. 615, no. 1-3, pp. 163-170. https://doi.org/10.1016/j.ejphar.2009.05.028

Long-term administration of nifedipine attenuates cardiac remodeling and diastolic heart failure in hypertensive rats. / Yamada, Takashi; Nagata, Kohzo; Cheng, Xian Wu; Obata, Koji; Saka, Masako; Miyachi, Masaaki; Naruse, Keiko; Nishizawa, Takao; Noda, Akiko; Izawa, Hideo; Kuzuya, Masafumi; Okumura, Kenji; Murohara, Toyoaki; Yokota, Mitsuhiro.

In: European Journal of Pharmacology, Vol. 615, No. 1-3, 01.08.2009, p. 163-170.

Research output: Contribution to journalArticle

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T1 - Long-term administration of nifedipine attenuates cardiac remodeling and diastolic heart failure in hypertensive rats

AU - Yamada, Takashi

AU - Nagata, Kohzo

AU - Cheng, Xian Wu

AU - Obata, Koji

AU - Saka, Masako

AU - Miyachi, Masaaki

AU - Naruse, Keiko

AU - Nishizawa, Takao

AU - Noda, Akiko

AU - Izawa, Hideo

AU - Kuzuya, Masafumi

AU - Okumura, Kenji

AU - Murohara, Toyoaki

AU - Yokota, Mitsuhiro

PY - 2009/8/1

Y1 - 2009/8/1

N2 - The Ca2+ channel blocker nifedipine has been reported to reduce the rate of new overt heart failure. We investigated the effects of nifedipine on left ventricular remodeling, oxidative stress, and gene expression in the failing heart of Dahl salt-sensitive (DS) rats. DS rats fed a high-salt diet from 7 weeks of age were treated with a non-antihypertensive (1 mg/kg per day, Nif-L) or mild-antihypertensive dose of nifedipine (3 mg/kg per day, Nif-H) or with vehicle (Vehicle) from 12 to 19 weeks. Marked left ventricular hypertrophy and fibrosis were apparent and the ratio of collagen type I to type III mRNA levels and the activity of matrix metalloproteinase (MMP)-2 and its mRNA expression in the myocardium were increased in Vehicle at 19 weeks in comparison with Control. Load-induced left ventricular hypertrophy was reduced in Nif-H, but not in Nif-L, relative to that in Vehicle. Treatment with either dose of nifedipine reduced the extent of fibrosis, the collagen type I to type III mRNA ratio, and MMP-2 activity and its mRNA expression compared with those in Vehicle. The decrease in the ratio of reduced to oxidized glutathione and the increase in NADPH oxidase activity apparent in the left ventricle of Vehicle were also inhibited by nifedipine at both doses. Nifedipine thus inhibited the development of left ventricular fibrosis and diastolic heart failure in DS rats, independently of its antihypertensive effect. The overall protective action of nifedipine is likely attributable to its antioxidant effect as well as to its antihypertensive action.

AB - The Ca2+ channel blocker nifedipine has been reported to reduce the rate of new overt heart failure. We investigated the effects of nifedipine on left ventricular remodeling, oxidative stress, and gene expression in the failing heart of Dahl salt-sensitive (DS) rats. DS rats fed a high-salt diet from 7 weeks of age were treated with a non-antihypertensive (1 mg/kg per day, Nif-L) or mild-antihypertensive dose of nifedipine (3 mg/kg per day, Nif-H) or with vehicle (Vehicle) from 12 to 19 weeks. Marked left ventricular hypertrophy and fibrosis were apparent and the ratio of collagen type I to type III mRNA levels and the activity of matrix metalloproteinase (MMP)-2 and its mRNA expression in the myocardium were increased in Vehicle at 19 weeks in comparison with Control. Load-induced left ventricular hypertrophy was reduced in Nif-H, but not in Nif-L, relative to that in Vehicle. Treatment with either dose of nifedipine reduced the extent of fibrosis, the collagen type I to type III mRNA ratio, and MMP-2 activity and its mRNA expression compared with those in Vehicle. The decrease in the ratio of reduced to oxidized glutathione and the increase in NADPH oxidase activity apparent in the left ventricle of Vehicle were also inhibited by nifedipine at both doses. Nifedipine thus inhibited the development of left ventricular fibrosis and diastolic heart failure in DS rats, independently of its antihypertensive effect. The overall protective action of nifedipine is likely attributable to its antioxidant effect as well as to its antihypertensive action.

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