title: Ion channel remodeling in cardiac hypertrophy is prevented by blood pressure reduction without affecting heart weight increase in rats with abdominal aortic banding.
abstract: This study investigates changes in the messenger RNA (mRNA) expression levels of HCN2 and HCN4 encoding rat If channels; ClC-3, a candidate gene for swelling-activated Cl- channel, and pICln, a regulatory subunit of Cl- channels in rat hypertrophied heart induced by banding the abdominal aorta. The mRNA expression levels were quantified with competitive reverse transcription polymerase chain reaction methods. Plasma renin activity, blood pressure, and heart weight increased. HCN2, HCN4, and ClC-3 mRNA levels decreased in the early phase after banding, whereas they increased in the late phase; pICln mRNA levels did not change at any stage. Administration of candesartan, an angiotensin II receptor blocker, prevented cardiac hypertrophy, but amlodipine, a Ca2+ channel blocker, did not prevent it, whereas both drugs lowered blood pressure. Changes in mRNA levels of HCN2, HCN4, and ClC-3 were alleviated by both candesartan and amlodipine, and these levels of the treated groups were not different from those in the sham control group. This study is the first to demonstrate changes in mRNA levels of HCN2, HCN4, and ClC-3 in cardiac hypertrophy induced by abdominal aortic banding. The data further suggest that the changes in channel mRNA levels were prevented by blood pressure reduction without affecting heart weight increase in this model.
authors.affiliation: Department of Cardiovascular Disease, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Hiramatsu
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Furukawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Sawanobori
authors.forename: Masayasu
authors.initials: M
authors.lastname: Hiraoka
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism; D018118:Chloride Channels / Q000096:biosynthesis; D054815:Cyclic Nucleotide-Gated Cation Channels; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D006973:Hypertension / Q000517:prevention & control*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000378:metabolism*; D007473:Ion Channels / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018118:Chloride Channels; C115376:ClC-3 channel; D054815:Cyclic Nucleotide-Gated Cation Channels; C578710:HCN2 protein, human; C119587:HCN4 protein, human; C578712:Hcn2 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009124:Muscle Proteins; D015221:Potassium Channels; D012333:RNA, Messenger