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

2000 ◽  
Vol 278 (6) ◽  
pp. H2050-H2056 ◽  
Author(s):  
Adviye Ergul ◽  
C. Allyson Walker ◽  
Aron Goldberg ◽  
Simona C. Baicu ◽  
Jennifer W. Hendrick ◽  
...  

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 ± 1 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 vs. 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.

2000 ◽  
Vol 6 (S2) ◽  
pp. 608-609
Author(s):  
J. Lin ◽  
C Wei

Endothelin-1 (ET-1) is a potent endothelial cell-drived vasoconstrictive peptide which is increased in congestive heart failure (CHF). ET-1 is converted from its precursor big ET-1 by activation of endothelin converting enzyme (ECE). ET-1 binding to ET-A receptor in vascular smooth muscle cells stimulates vasoconstriction and binding to ET-B receptor in vascular endothelial cells mediates vasodilation. In previous studies, we and others demonstrated that plasma ET-1 was significantly increased in congestive heart failure. However, the presentation and localization of endothelin converting enzyme and endothelin receptors (ET-A and ET-B) in human cardiac tissue with and without heart failure remain unclear. Therefore, the current study was designed to investigate the expression and localization of endothelin receptors and endothelin converting enzyme in human myocardium in the absence or presence of congestive heart failure.Human atrial tissues (n=6) were obtained from normal subjects and end-stage CHF patients during cardiac transplantation. The expression of ECE, ET-A and ET-B were determined by immunohistochemical staining (IHCS).


1995 ◽  
Vol 51 (3) ◽  
pp. 267-272 ◽  
Author(s):  
Pascal de Groote ◽  
Alain Millaire ◽  
André Racadot ◽  
Eric Decoulx ◽  
Gérard Ducloux

1997 ◽  
Vol 79 (9) ◽  
pp. 1261-1263 ◽  
Author(s):  
Enrico Mangieri ◽  
Gaetano Tanzilli ◽  
Francesco Barillà ◽  
Massimo Ciavolella ◽  
Gianluca Serafini ◽  
...  

1996 ◽  
Vol 148 (1) ◽  
pp. 51-57 ◽  
Author(s):  
C Azizi ◽  
G Maistre ◽  
H Kalotka ◽  
R Isnard ◽  
C Barthélemy ◽  
...  

Abstract A specific and sensitive radioimmunoassay (RIA) for the N-terminal fragment of proatrial natriuretic peptide (NproANP) was developed. Antiserum raised in rabbits against a mixture enriched with prohormone was 100% cross-reactive with human proANP(1–30). Plasma concentrations of proANP(1–30) and ANP immunoreactivities (ir-) were simultaneously measured in healthy subjects and patients with congestive heart failure (CHF; 26 dilated cardiomyopathy and 5 ischemic heart disease). High plasma levels of both ir-proANP(1–30) and ir-ANP were detected in CHF patients. Circulating ir-ANP levels were elevated in New York Heart Association functional Classes II and III patients but not in Class I patients. However, plasma levels of ir-proANP(1–30) were higher in asymptomatic patients than in healthy subjects, and markedly increased in patients of Classes II and III. Analysis of ir-proANP(1–30) by gel filtration chromatography or reverse-phase high pressure liquid chromatography revealed a 10 kDa peptide circulating as a distinct entity. These findings indicate that: (i) the most probable form of NproANP in human plasma is a 10 kDa peptide and (ii) in CHF patients the rise in plasma ir-proANP(1–30) levels is more pronounced than the variation in plasma ir-ANP. Thus, NproANP plasma levels may prove to be a more sensitive marker of left ventricular dysfunction than ANP. Journal of Endocrinology (1996) 148, 51–57


2003 ◽  
Vol 41 (6) ◽  
pp. 266 ◽  
Author(s):  
Kenneth Dickstein ◽  
Hanka de Voogd ◽  
Milutin Miric ◽  
Roland Willenbrock ◽  
Veselin Mitrovic ◽  
...  

Circulation ◽  
1999 ◽  
Vol 99 (4) ◽  
pp. 570-577 ◽  
Author(s):  
Atsuyuki Wada ◽  
Takayoshi Tsutamoto ◽  
Masato Ohnishi ◽  
Masahide Sawaki ◽  
Daisuke Fukai ◽  
...  

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