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

Research output: Contribution to journalArticle

36 Citations (Scopus)

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

Fingerprint

Endothelin-1
Muscle Cells
Heart Failure
Endothelin-Converting Enzymes
Microdialysis
Myocardium
Swine

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).

ET-1 in the myocardial interstitium : Relation to myocyte ECE activity and expression. / Ergul, Adviye; Walker, C. Allyson; Goldberg, Aron; Baicu, Simona C.; Hendrick, Jennifer W.; King, Mary K.; Spinale, Francis G.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 278, No. 6 47-6, 01.06.2000.

Research output: Contribution to journalArticle

Ergul, A, Walker, CA, Goldberg, A, Baicu, SC, Hendrick, JW, King, MK & Spinale, FG 2000, 'ET-1 in the myocardial interstitium: Relation to myocyte ECE activity and expression', American Journal of Physiology - Heart and Circulatory Physiology, vol. 278, no. 6 47-6.
Ergul, Adviye ; Walker, C. Allyson ; Goldberg, Aron ; Baicu, Simona C. ; Hendrick, Jennifer W. ; King, Mary K. ; Spinale, Francis G. / ET-1 in the myocardial interstitium : Relation to myocyte ECE activity and expression. In: American Journal of Physiology - Heart and Circulatory Physiology. 2000 ; Vol. 278, No. 6 47-6.
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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.",
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AU - Spinale, Francis G.

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AB - 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.

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