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

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 (AT 2 ) receptor between SCASMCs of control and Iso-induced hypertrophied model, the expression of Ang II type 1 (AT 1 ) receptor and phosphorylated PKCα 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 AT 1 receptor and the activation of PKCα. 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.