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

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.