Effect of fosinopril on the transient outward potassium current of hypertrophied left ventricular myocardium in the spontaneously hypertensive rat.
To investigate fosinopril's effect on the transient outward potassium current (Ito) of differing degrees of hypertrophied myocytes in the spontaneously hypertensive rat (SHR). Ten- and 24-week-old SHRs were used as models for cardiac hypertrophy. Hypertrophied ventricular myocytes were exposed to 1, 10, and 100 μmol/L fosinopril; the whole-cell patch-clamp technique was used to study the effects on the transient outward potassium current. Ito current density was decreased in SHR myocytes relative to controls (14.17 ± 0.31 and 11.62 ± 0.08 pA/pF in 10- and 24-week-old SHR versus 16.73 ± 0.15 pA/pF, p < 0.01). Higher concentrations of fosinopril (10 and 100 μmol/L) increased Ito peak current density in 10-week-old SHR myocytes compared with controls (14.92 ± 0.14 and 15.27 ± 0.13 pA/pF versus 14.17 ± 0.31 pA/pF, p < 0.01). Fosinopril increased Ito peak current density in 24-week-old SHR myocytes at all doses (12.70 ± 0.07, 13.74 ± 0.10, and 14.53 ± 0.13 versus 11.62 ± 0.08 pA/pF for controls, p < 0.01). Fosinopril had a greater Ito elevation potential on hypertrophied myocytes in 24-week-old compared with 10-week-old SHR for each dose (1.08 ± 0.09 versus 0.37 ± 0.26 pA/pF, p < 0.01; 2.13 ± 0.05 versus 0.75 ± 0.35 pA/pF, p < 0.01; 2.92 ± 0.07 versus 1.10 ± 0.40 pA/pF, p < 0.01). Fosinopril increased Ito current density in hypertrophied myocytes. This effect was more pronounced in myocytes with a greater degree of hypertrophy.
Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.
Zhi-Bin
ZB
Huang
Chang
C
Fang
Mao-Huan
MH
Lin
Gui-Yi
GY
Yuan
Shu-Xian
SX
Zhou
Wei
W
Wu
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D017328:Fosinopril / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D015221:Potassium Channels; D017328:Fosinopril