Altered inotropic response of endothelin-1 in cardiomyocytes from rats with isoproterenol-induced cardiomyopathy.
Altered inotropic response of endothelin-1 in cardiomyocytes from rats with isoproterenol-induced cardiomyopathy.
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DOI：
10.1016/s0008-6363(98)00166-7
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发表时间：
1998-09
影响因子：
10.8
通讯作者：
M. Suzuki;N. Ohte;Z. Wang;D. Williams;W. Little;C. Cheng
中科院分区：
文献类型：
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作者：
M. Suzuki;N. Ohte;Z. Wang;D. Williams;W. Little;C. Cheng
Objective:The positive inotropic effect of endothelin-1 (ET-1) on normal myocardial contraction may be altered in pathological states. The purpose of this study was to assess the direct effect of ET-1 on cardiomyocyte performance and its cellular mechanism in congestive heart failure (CHF).Methods:We measured the plasma levels of ET-1 and compared the effects of ET-1 (10−10–10−8M) on contractile performance and the [Ca2+]itransient in the myocytes of left ventricles (LV) from 15 age-matched normal adult rats and 15 rats with isoproterenol (ISO)-induced CHF.Results:With CHF, the plasma levels of ET-1 (19.7±6.3 vs. 4.1±0.5 fmol/ml,p<0.05) were markedly elevated. In normal myocytes, superfusion of ET-1 caused significant increases in the systolic amplitude (SA, 8–16%) and the peak velocity of shortening (dL/dtmax, 20–35%;p<0.01) without causing a change in the peak [Ca2+]itransient. In contrast, in myocytes from CHF rats, ET-1 produced significant reductions in SA (9–13%) and in the velocity of relengthening, dR/dtmax(10–14%;p<0.05). The myocytes' dR/dtmaxalso decreased by 8–10% (p<0.05). These changes were associated with a significant decrease in the peak [Ca2+]itransient (20–23%,p<0.0 1). These responses to ET-1 were abolished by the incubation of myocytes with an ETAreceptor antagonist (BQ123) or a protein kinase C (PKC) inhibitor (H-7 or staurosporine).Conclusion:ISO-induced CHF is associated with elevated plasma ET-1 and an altered cardiomyocyte response to ET-1. After CHF, ET-1 produces a direct depression of cardiomyocyte contractile performance that is associated with a significant decrease in the peak [Ca2+]itransient. These effects are likely to be mediated through ETAreceptors and involve the PKC pathway.
