title: Endothelin receptor pathway in human left ventricular myocytes: relation to contractility.
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) undergoing 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 micromol/L), the sodium/hydrogen (Na/H) exchanger (EIPA, 1 micromol/L), both PKC and the Na/H exchanger, or the ET(A) receptor (BQ-123, 1 micromol/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.
authors.affiliation: Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29403, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Goldberg
authors.forename: B R
authors.initials: BR
authors.lastname: Bond
authors.forename: R
authors.initials: R
authors.lastname: Mukherjee
authors.forename: R B
authors.initials: RB
authors.lastname: New
authors.forename: J L
authors.initials: JL
authors.lastname: Zellner
authors.forename: F A
authors.initials: FA
authors.lastname: Crawford
authors.forename: F G
authors.initials: FG
authors.lastname: Spinale
mesh_terms: D002478:Cells, Cultured; D006352:Heart Ventricles / Q000166:cytology*; D006801:Humans; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017466:Receptors, Endothelin / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors
chemical_list: D017466:Receptors, Endothelin; D017923:Sodium-Hydrogen Exchangers; D011493:Protein Kinase C