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

28Citations
Citations of this article
11Readers
Mendeley users who have this article in their library.

Abstract

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.

Cite

CITATION STYLE

APA

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

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free