Endothelin isoforms and the response to myocardial stretch

Irene L. Ennis, Carolina D. Garciarena, Néstor G. Pérez, Raúl A. Dulce, María C. Camilión De Hurtado, Horacio E. Cingolani

Research output: Contribution to journalArticle

Abstract

Myocardial stretch elicits a biphasic increase in developed force with a first rapid force response and a second slow force response (SFR). The rapid phase is due to an increase in myofilament Ca2+ responsiveness; the SFR, analyzed here, is ascribed to a progressive increase in Ca2+ transients. Experiments were performed in cat papillary muscles to further elucidate the signaling pathway underlying the SFR. Although the SFR was diminished by BQ-123, a similar endothelin (ET)-1-induced increase in force was not affected: 23 ± 2 vs. 23 ± 3% (not significant). Instead, BQ-123 suppressed the contractile effects of ET-2 or ET-3 (21 ± 2 and 25 ± 3% vs. -1 ± 1 and -7 ± 3% respectively, P <0.05), suggesting that ET-2 or ET-3, but not ET-1, was involved in the SFR. Each isoform activated the Na+/H+ exchanger (NHE-1), increasing intracellular Na+ concentration by 2.0 ± 0.1, 2.3 ± 0.1, and 2.1 ± 0.4 mmol/l for ET-1, ET-2, and ET-3, respectively (P <0.05). The NHE-1 inhibitor HOE-642 prevented the increases in force and intracellular Na+ concentration induced by all the ET isoforms, but only ET-2 and ET-3 effects were sensitive to BQ-123. Real-time RT-PCR measurements of prepro-ET-1, -ET-2, and -ET-3 were performed before and 5, 15, and 30 min after stretch. No changes in ET-1 or ET-2, but an increase of ∼60% in ET-3, mRNA after 15 min of stretch were detected. Stretch-induced ET-3 mRNA upregulation and its mechanical counterpart were suppressed by AT 1 receptor blockade with losartan. These data suggest a role for AT1-mediated ET-3 released in the early activation of NHE-1 that follows myocardial stretch.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number6 57-6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Endothelin-3
Endothelins
Endothelin-2
Protein Isoforms
Endothelin-1
Messenger RNA
Sodium-Hydrogen Antiporter
Losartan
Papillary Muscles
Myofibrils
Real-Time Polymerase Chain Reaction
Cats
Up-Regulation

Keywords

  • Endothelin isoforms
  • Myocardial contractility
  • Signal transduction
  • Sodium/hydrogen exchanger-1

ASJC Scopus subject areas

  • Physiology

Cite this

Ennis, I. L., Garciarena, C. D., Pérez, N. G., Dulce, R. A., Camilión De Hurtado, M. C., & Cingolani, H. E. (2005). Endothelin isoforms and the response to myocardial stretch. American Journal of Physiology - Heart and Circulatory Physiology, 288(6 57-6). https://doi.org/10.1152/ajpheart.01202.2004

Endothelin isoforms and the response to myocardial stretch. / Ennis, Irene L.; Garciarena, Carolina D.; Pérez, Néstor G.; Dulce, Raúl A.; Camilión De Hurtado, María C.; Cingolani, Horacio E.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 6 57-6, 06.2005.

Research output: Contribution to journalArticle

Ennis, IL, Garciarena, CD, Pérez, NG, Dulce, RA, Camilión De Hurtado, MC & Cingolani, HE 2005, 'Endothelin isoforms and the response to myocardial stretch', American Journal of Physiology - Heart and Circulatory Physiology, vol. 288, no. 6 57-6. https://doi.org/10.1152/ajpheart.01202.2004
Ennis IL, Garciarena CD, Pérez NG, Dulce RA, Camilión De Hurtado MC, Cingolani HE. Endothelin isoforms and the response to myocardial stretch. American Journal of Physiology - Heart and Circulatory Physiology. 2005 Jun;288(6 57-6). https://doi.org/10.1152/ajpheart.01202.2004
Ennis, Irene L. ; Garciarena, Carolina D. ; Pérez, Néstor G. ; Dulce, Raúl A. ; Camilión De Hurtado, María C. ; Cingolani, Horacio E. / Endothelin isoforms and the response to myocardial stretch. In: American Journal of Physiology - Heart and Circulatory Physiology. 2005 ; Vol. 288, No. 6 57-6.
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