title: Irbesartan-mediated AT1 receptor blockade attenuates hyposmotic-induced enhancement of I Ks current and prevents shortening of action potential duration in atrial myocytes.
abstract: BACKGROUND
  Stretch of the atrial membrane upregulates the slow component of delayed rectifier K(+) current (I(Ks)). Blockade of angiotensin II subtype 1 receptors (AT(1)R) attenuates this increase in I(Ks). The present study aimed to examine the effects of irbesartan, a selective AT(1)R blocker (ABR), on both the enhancement of I(Ks) and the shortening of action potential duration (APD) induced by stretching atrial myocytes for exploring the mechanisms underlying the prevention of atrial fibrillation (AF) by ABR.
  
  
  METHODS
  Hyposmotic solution (Hypo-S) was used to stretch guinea pig atrial myocytes. I(Ks) and APD were recorded using the whole-cell patch-clamp technique.
  
  
  RESULTS
  Irbesartan (1-50 μM) attenuated the Hypo-S-induced increase in I(Ks) and shortening of APD90. Hypo-S increased the I(Ks) by 113.4%, whereas Hypo-S + 1 μM irbesartan and Hypo-S + 50 μM irbesartan increased the I(Ks) by only 74.5% and 70.3%, respectively. In addition, Hypo-S shortened the APD(90) by 19.0%, whereas Hypo-S + 1 μM irbesartan and Hypo-S + 50 μM irbesartan shortened the APD90 by 12.1% and 12.0%, respectively.
  
  
  CONCLUSIONS
  The actions of irbesartan on electrical changes induced by stretching atrial myocytes are associated with blocking AT(1)R. These actions may be beneficial for treating AF.
authors: Department of Pharmacology, Medical School of Xi'an Jiaotong University, PR China Department of Physiology, Shiga University of Medical Science, Japan Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Japan.
authors: Jie
authors: J
authors: Wu
authors: Department of Physiology, Shiga University of Medical Science, Japan.
authors: Wei-Guang
authors: WG
authors: Ding
authors: Department of Pharmacology, Medical School of Xi'an Jiaotong University, PR China.
authors: Jin
authors: J
authors: Zhao
authors: Department of Pharmacology, Medical School of Xi'an Jiaotong University, PR China.
authors: Wei-Jin
authors: WJ
authors: Zang
authors: Department of Physiology, Shiga University of Medical Science, Japan.
authors: Hiroshi
authors: H
authors: Matsuura
authors: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Japan horie@belle.shiga-med.ac.jp.
authors: Minoru
authors: M
authors: Horie
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D006168:Guinea Pigs; D007038:Hypotonic Solutions / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects*; D000077405:Irbesartan; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D007038:Hypotonic Solutions; D015221:Potassium Channels; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000077405:Irbesartan
keywords: Angiotensin II type 1 receptor; I
                 Ks; action potential; atrial myocytes; irbesartan