Endothelin receptor pathway in human left ventricular myocytes: Relation to contractility

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Background. Increased synthesis and release of the potent bioactive peptide endothelin-1 (ET-1) occurs during and after cardiac surgery. However, the cellular and molecular basis for the effects of ET-1 on human left ventricular (LV) myocyte contractility remains unknown. Methods. LV myocyte contractility was examined from myocardial biopsies taken from patients (n = 30) under-going elective coronary artery bypass. LV myocytes (n = 997, > 30/patient) were isolated using microtrituration and contractility examined by videomicroscopy at baseline and after ET-1 exposure (200 pmol/L). In additional studies, myocytes were pretreated to inhibit either protein kinase C (PKC) (chelerythrine, 1 μmol/L), the sodium/hydrogen (Na/H) exchanger (EIPA, 1 μmol/L), both PKC and the Na/H exchanger, or the ETΛ receptor (BQ-123, 1 μmol/L), followed. with ET-1 exposure. Results. Basal myocyte shortening increased 37.8 ± 6.3% with ET-1 (p < 0.05). Na/H exchanger, PKC, and dual inhibition all eliminated the effects of ET-1. Furthermore, ET(A) inhibition demonstrated that ET-1 effects on myocyte contractility were mediated through the ET(A) receptor subtype. Conclusions. ET-1 directly influences human LV myocyte contractility, which is mediated through the ET(A) receptor and requires intracellular activation of PKC and stimulation of the Na/H exchanger. (C) 2000 by The Society of Thoracic Surgeons.




Goldberg, A. T., Bond, B. R., Mukherjee, R., New, R. B., Zellner, J. L., Crawford, F. A., & Spinale, F. G. (2000). Endothelin receptor pathway in human left ventricular myocytes: Relation to contractility. Annals of Thoracic Surgery, 69(3), 711–715. https://doi.org/10.1016/S0003-4975(99)01515-5

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