PULMONARY AND CARDIAC EXPRESSION OF PREPROENDOTHELIN-1 MESSENGER-RNA ARE INCREASED IN HEART-FAILURE AFTER MYOCARDIAL-INFARCTION IN RATS - LOCALIZATION OF PREPROENDOTHELIN-1 MESSENGER-RNA AND ENDOTHELIN PEPTIDE
T. Tonnessen et al., PULMONARY AND CARDIAC EXPRESSION OF PREPROENDOTHELIN-1 MESSENGER-RNA ARE INCREASED IN HEART-FAILURE AFTER MYOCARDIAL-INFARCTION IN RATS - LOCALIZATION OF PREPROENDOTHELIN-1 MESSENGER-RNA AND ENDOTHELIN PEPTIDE, Cardiovascular Research, 39(3), 1998, pp. 633-643
Objectives: Recent reports indicate that endothelin (ET) plays an impo
rtant pathophysiological role in congestive heart failure (CHF). Howev
er, existing data on local cardiopulmonary ET production are few. No s
tudies have hitherto examined the specific anatomic localization of ca
rdiopulmonary ET synthesis in CHF. Thus, the aims of the present study
were to examine whether cardiopulmonary preproET-l mRNA synthesis is
upregulated in CHF and to determine the anatomic localization of prepr
oET-l mRNA and the mature peptide. Methods: CHF was induced in rats by
occluding the left coronary artery. Only animals with a left ventricu
lar end-diastolic pressure above 15 mmHg after one week were included
(n=28). Sham-operated animals served as controls (n=24). Hearts and lu
ngs were examined by mRNA slot blot analyses, in situ hybridization (I
SH) and immunohistochemistry (MC). Results: In CHF-rats, slot blot ana
lyses revealed a 3.5+/-1.1-fold and a 6.4+/-0.8-fold upregulation of p
reproET-l mRNA in the noninfarcted and the infarcted area of the left
ventricles, respectively (p<0.05 for both). ISH revealed that the prep
roET-l mRNA was localized predominantly over the granulation tissue in
the infarcted region. The ET peptide was predominantly localized to i
nflammatory cells and remaining cardiomyocytes in the infarcted region
as determined by IHC. Lungs from CHF-rats showed a 1.5+/-0.1-fold upr
egulation of preproET-l mRNA (p=0.01). The most abundant preproET-l mR
NA and ET-l-like-immunoreactivity (ET-l-ir) was seen over inflammatory
cells and over airway epithelial cells. Some ET-l-ir was also located
to bronchial and vascular smooth muscle cells. Conclusion: Increased
cardiopulmonary ET synthesis strongly suggest a pathophysiological rol
e for ET in CHF. (C) 1998 Elsevier Science B.V. All rights reserved.