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

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.

• Authors: 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
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 615 Issue 1-3 Pg. 163-70 (Aug 01 2009) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 19501083 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Calcium Channel Blockers
• Collagen
• NADPH Oxidases
• Matrix Metalloproteinase 2
• Glutathione
• Nifedipine

Topics

• Animals
• Antihypertensive Agents (pharmacology, therapeutic use)
• Calcium Channel Blockers (pharmacology, therapeutic use)
• Collagen (metabolism)
• Disease Models, Animal
• Fibrosis
• Glutathione (metabolism)
• Heart Failure, Diastolic (drug therapy, pathology, physiopathology)
• Hypertension (drug therapy, pathology, physiopathology)
• Hypertrophy, Left Ventricular (drug therapy, pathology, physiopathology)
• Infusions, Subcutaneous
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Myocardium (metabolism, pathology)
• NADPH Oxidases (metabolism)
• Nifedipine (pharmacology, therapeutic use)
• Oxidative Stress (drug effects)
• Rats
• Rats, Inbred Dahl
• Ventricular Remodeling (drug effects)