Increased inhibition of inward rectifier K+ channels by angiotensin II in small-diameter coronary artery of isoproterenol-induced hypertrophied model

Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1768-75. doi: 10.1161/ATVBAHA.107.143339. Epub 2007 May 24.

Abstract

Objective: We investigated the effects of angiotensin II (Ang II) on inward rectifier K+ (Kir) channels in small-diameter coronary arterial smooth muscle cells (SCASMCs) of control and isoproterenol (Iso)-induced hypertrophied rabbits.

Methods and results: Kir current amplitude and Kir channel protein expression were definitely lower in the Iso-induced hypertrophied model than in the control. In a pressurized arterial experiment, 15 mmol/L K+-induced vasodilation was greater in the control arteries than in the arteries of Iso-induced hypertrophied model. Ang II reduced the Kir current in a concentration-dependent manner, and this inhibition was greater in SCASMCs from Iso-induced hypertrophied model than from control. Although, there was no difference in the expression of Ang II type 2 (AT2) receptor between SCASMCs of control and Iso-induced hypertrophied model, the expression of Ang II type 1 (AT1) receptor and phosphorylated PKC alpha were greater in SCASMCs of Iso-induced hypertrophied model than of control.

Conclusion: Ang II inhibits Kir channels more prominently in SCASMCs of Iso-induced hypertrophied model owing to increases in the expression of AT1 receptor and the activation of PKC alpha. Our findings about the differential expression of Kir channels and different modulation of Kir channels by a vasoconstrictor (Ang II) in a hypertrophy model are important for better understanding the responsiveness of small-diameter arteries during hypertrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Blotting, Western
  • Cardiomyopathy, Hypertrophic / pathology
  • Cells, Cultured
  • Coronary Vessels / cytology*
  • Disease Models, Animal
  • Electrophysiology
  • Endothelium, Vascular / pathology
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Potassium Channels, Inwardly Rectifying / drug effects*
  • Potassium Channels, Inwardly Rectifying / metabolism*
  • Probability
  • Rabbits
  • Random Allocation
  • Reference Values
  • Sensitivity and Specificity
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation / drug effects
  • Vasodilation / physiology

Substances

  • Potassium Channels, Inwardly Rectifying
  • Vasoconstrictor Agents
  • Angiotensin II