Endothelin receptor pathway in human left ventricular myocytes: relation to contractility
| Autor: | James L. Zellner, Aron T. Goldberg, Brian R. Bond, Rupak Mukherjee, Fred A. Crawford, Francis G. Spinale, R.Brent New |
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| Rok vydání: | 2000 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Sodium-Hydrogen Exchangers Heart Ventricles Stimulation Peptide hormone Contractility chemistry.chemical_compound Internal medicine medicine Humans Myocyte Receptor Cells Cultured Protein Kinase C Protein kinase C Receptors Endothelin business.industry Middle Aged Myocardial Contraction Endocrinology Chelerythrine chemistry Surgery Cardiology and Cardiovascular Medicine business Endothelin receptor |
| Zdroj: | The Annals of Thoracic Surgery. 69:711-715 |
| ISSN: | 0003-4975 |
| DOI: | 10.1016/s0003-4975(99)01515-5 |
| Popis: | 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.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.Basal myocyte shortening increased 37.8 +/- 6.3% with ET-1 (p0.05). 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.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. |
| Databáze: | OpenAIRE |
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