Effect of fosinopril on the transient outward potassium current of hypertrophied left ventricular myocardium in the spontaneously hypertensive rat

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 387; no. 5; pp. 419 - 425
• Main Authors: Zhi-bin, Huang, Chang, Fang, Mao-huan, Lin, Gui-yi, Yuan, Shu-xian, Zhou, Wei, Wu
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2014; Springer Nature B.V
• Subjects: Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Biomedical and Life Sciences; Biomedicine; Fosinopril - pharmacology; Hypertension - drug therapy; Hypertension - metabolism; Hypertrophy, Left Ventricular - metabolism; Male; Myocardium - metabolism; Neurosciences; Original Article; Pharmacology/Toxicology; Potassium Channels - drug effects; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Hypertension; Hypertrophied myocytes; Fosinopril; Transient outward potassium current
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-014-0956-6

To investigate fosinopril’s effect on the transient outward potassium current (I to ) 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. I to 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 I to 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 I to 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 I to 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 I to current density in hypertrophied myocytes. This effect was more pronounced in myocytes with a greater degree of hypertrophy.