Modulation of the transient outward K+ current by inhibition of endothelin-A receptors in normal and hypertrophied rat hearts.
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Modulation of the transient outward K+ current by inhibition of endothelin-A receptors in normal and hypertrophied rat hearts. / Wagner, Michael E.; Goltz, Diane; Stucke, Carolin; Schwoerer, Alexander; Ehmke, Heimo; Volk, Tilmann.
in: PFLUG ARCH EUR J PHY, Jahrgang 454, Nr. 4, 4, 2007, S. 595-604.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Modulation of the transient outward K+ current by inhibition of endothelin-A receptors in normal and hypertrophied rat hearts.
AU - Wagner, Michael E.
AU - Goltz, Diane
AU - Stucke, Carolin
AU - Schwoerer, Alexander
AU - Ehmke, Heimo
AU - Volk, Tilmann
PY - 2007
Y1 - 2007
N2 - Inhibition of endothelin-A (ET(A)) receptors has been shown to reduce ventricular electrical abnormalities associated with cardiac failure. In this study, we investigate the effect of ET(A)-receptor inhibition on the development of regional alterations of the transient outward K(+) current (I (to)) in the setting of pressure-induced left ventricular (LV) hypertrophy. Cardiac hypertrophy was induced in female Sprague-Dawley rats by stenosis of the ascending aorta (AS) for 7 days. Treatment with the selective ET(A)-receptor antagonist darusentan (LU135252, 35 mg [kg body weight](-1) day(-1)) was started 1 day before the surgery. AS induced a 46% increase in the relative LV weight (p <0.001) and caused a significant reduction in I (to) (at +40 mV) in epicardial myocytes (19.5 +/- 1.2 pA pF(-1), n = 32 vs 23.2 +/- 1.2 pA pF(-1), n = 35, p <0.05). Darusentan further reduced I (to) in AS (15.4 +/- 1.3 pA pF(-1), n = 37, p <0.05) and sham-operated animals (19.8 +/- 1.6 pA pF(-1), n = 48, ns.). The effects of AS and darusentan on I (to) were significant and independent as tested by two-way analysis of variance. I (to) was not affected in endocardial myocytes. These results indicate that endothelin-1 may exert a tonic effect on the magnitude of I (to) in the epicardial region of the left ventricle but that ET(A)-receptor activation is not necessary for the development of electrical alterations associated with pressure-induced hypertrophy.
AB - Inhibition of endothelin-A (ET(A)) receptors has been shown to reduce ventricular electrical abnormalities associated with cardiac failure. In this study, we investigate the effect of ET(A)-receptor inhibition on the development of regional alterations of the transient outward K(+) current (I (to)) in the setting of pressure-induced left ventricular (LV) hypertrophy. Cardiac hypertrophy was induced in female Sprague-Dawley rats by stenosis of the ascending aorta (AS) for 7 days. Treatment with the selective ET(A)-receptor antagonist darusentan (LU135252, 35 mg [kg body weight](-1) day(-1)) was started 1 day before the surgery. AS induced a 46% increase in the relative LV weight (p <0.001) and caused a significant reduction in I (to) (at +40 mV) in epicardial myocytes (19.5 +/- 1.2 pA pF(-1), n = 32 vs 23.2 +/- 1.2 pA pF(-1), n = 35, p <0.05). Darusentan further reduced I (to) in AS (15.4 +/- 1.3 pA pF(-1), n = 37, p <0.05) and sham-operated animals (19.8 +/- 1.6 pA pF(-1), n = 48, ns.). The effects of AS and darusentan on I (to) were significant and independent as tested by two-way analysis of variance. I (to) was not affected in endocardial myocytes. These results indicate that endothelin-1 may exert a tonic effect on the magnitude of I (to) in the epicardial region of the left ventricle but that ET(A)-receptor activation is not necessary for the development of electrical alterations associated with pressure-induced hypertrophy.
M3 - SCORING: Zeitschriftenaufsatz
VL - 454
SP - 595
EP - 604
JO - PFLUG ARCH EUR J PHY
JF - PFLUG ARCH EUR J PHY
SN - 0031-6768
IS - 4
M1 - 4
ER -
