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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.
AuthorsMikio Hiramatsu, Tetsushi Furukawa, Tohru Sawanobori, Masayasu Hiraoka
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 39 Issue 6 Pg. 866-74 (Jun 2002) ISSN: 0160-2446 [Print] United States
PMID12021581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chloride Channels
  • ClC-3 channel
  • Cyclic Nucleotide-Gated Cation Channels
  • HCN2 protein, human
  • HCN4 protein, human
  • Hcn2 protein, rat
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels
  • Muscle Proteins
  • Potassium Channels
  • RNA, Messenger
Topics
  • Animals
  • Aorta, Abdominal (metabolism)
  • Chloride Channels (biosynthesis)
  • Cyclic Nucleotide-Gated Cation Channels
  • Heart (physiology, physiopathology)
  • Heart Ventricles (metabolism)
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Hypertension (prevention & control)
  • Hypertrophy, Left Ventricular (drug therapy, metabolism)
  • Ion Channels (biosynthesis, metabolism)
  • Male
  • Muscle Proteins
  • Organ Size (drug effects, physiology)
  • Potassium Channels
  • RNA, Messenger (biosynthesis)
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction

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