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Endothelin-1 in heart and pulmonary tissue in experimental heart failure
M L Sirviö1, K Helin, P Stewen
1Unit of Clinical Physiology, Minerva Foundation, Helsinki, Finland.
Insights
Congestive heart failure (CHF) increases levels of endothelin 1 (ET-1) in lung and right ventricle tissues. This enhanced ET-1 production may contribute to pulmonary vascular resistance in CHF patients.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Pathophysiology
Background:
- Congestive heart failure (CHF) is a complex syndrome affecting cardiac function.
- Endothelin 1 (ET-1) is a potent vasoconstrictor peptide implicated in cardiovascular diseases.
- The role of ET-1 in the specific tissue alterations during CHF requires further elucidation.
Purpose of the Study:
- To investigate the impact of experimentally induced CHF on tissue levels of ET-1 and its precursor mRNA (prepro-ET-1) in rats.
- To determine the specific cardiac and pulmonary compartments affected by these changes.
Main Methods:
- Congestive heart failure (CHF) was induced in rats via left coronary artery ligation.
- Tissue levels of ET-1 were quantified using radioimmunoassay.
- Prepro-ET-1 mRNA levels were assessed via quantitative polymerase chain reaction.
- Cardiac and pulmonary tissues, along with plasma atrial natriuretic peptide, were analyzed three weeks post-ligation.
Main Results:
- Rats with CHF exhibited increased heart weight/body weight ratio and elevated plasma atrial natriuretic peptide.
- Pulmonary tissue showed a 3.6-fold increase in ET-1 concentration.
- The right ventricle displayed a 1.4-fold increase in ET-1 concentration, while the left ventricle did not show significant changes.
- Prepro-ET-1 mRNA levels mirrored the observed ET-1 concentration patterns.
Conclusions:
- Experimentally induced CHF leads to enhanced ET-1 production in pulmonary and right ventricular tissues.
- Elevated ET-1 in these tissues may play a significant role in the development of high pulmonary vascular resistance associated with CHF.
- These findings highlight a potential therapeutic target for managing CHF complications.
Abstract:
We studied the effect of congestive heart failure (CHF) on the tissue levels of endothelin 1 (ET-1) and of the mRNA of prepro-ET-1 in the rat. Congestive heart failure was produced by ligation of the left coronary artery. The rats were killed 3 weeks after the ligation. Congestive heart failure was determined by elevated plasma atrial natriuretic peptide and by a myocardial infarction scar covering more than 30% of the left ventricular circumference. Both ET-1 and prepro-ET-1 mRNA were measured in cardiac ventricles and lungs by radioimmunoassay and quantitative polymerase chain reaction. The rats with CHF had an increased heart weight/body weight ratio and elevated plasma atrial natriuretic peptide levels. In rats with CHF, as compared to controls, the concentration of ET-1 was elevated 3.6-fold in pulmonary tissue and 1.4-fold in the right ventricle, respectively, but not in the left ventricle. The concentration of mRNA showed a similar pattern, but due to methodological limitations this was assumed to represent a rough estimate only. The enhanced production of ET-1 in the right ventricle and in the pulmonary tissue may be of pathophysiological importance for the development of high pulmonary vascular resistance in CHF.