ET-1 in the myocardial interstitium: Relation to myocyte ECE activity and expression

Adviye Ergul, C. Allyson Walker, Aron Goldberg, Simona C. Baicu, Jennifer W. Hendrick, Mary K. King, Francis G. Spinale

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Abstract

Increased plasma levels of endothelin-1 (ET-1) have been identified in congestive heart failure (CHF), but local myocardial interstitial ET-1 levels and the relation to determinants of ET-1 synthesis remain to be defined. Accordingly, myocardial interstitial ET-1 levels and myocyte endothelin- converting enzyme (ECE)-1 activity and expression with the development of CHF were examined. Pigs were instrumented with a microdialysis system to measure myocardial interstitial ET-1 levels with pacing CHF (240 beats/min, 3 wk; n = 9) and in controls (n = 14). Plasma ET-1 was increased with CHF (15 ± 1 vs. 9 ± I fmol/ml, P < 0.05) as was total myocardial ET-1 content (90 ± 15 vs. 35 ± 5 fmol/g, P < 0.05). Paradoxically, myocardial interstitial ET-1 was decreased in CHF (32 ± 4 rs. 21 ± 2 fmol/ml, P < 0.05), which indicated increased ET-1 uptake by the left ventricular (LV) myocardium with CHF. In isolated LV myocyte preparations, ECE-1 activity was increased by twofold with CHF (P < 0.05). In LV myocytes, both ECE-1a and ECE-1c mRNAs were detected, and ECE-1a expression was upregulated fivefold in CHF myocytes (P < 0.05). In conclusion, this study demonstrated compartmentalization of ET-1 in the myocardial interstitium and enhanced ET-1 uptake with CHF. Thus a local ET-1 system exists at the level of the myocyte, and determinants of ET-1 biosynthesis are selectively regulated within this myocardial compartment in CHF.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume278
Issue number6 47-6
StatePublished - Jun 1 2000

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Keywords

  • Congestive heart failure
  • Endothelin-1
  • Endothelin-converting enzyme
  • Interstitial fluid

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Ergul, A., Walker, C. A., Goldberg, A., Baicu, S. C., Hendrick, J. W., King, M. K., & Spinale, F. G. (2000). ET-1 in the myocardial interstitium: Relation to myocyte ECE activity and expression. American Journal of Physiology - Heart and Circulatory Physiology, 278(6 47-6).