Increased cardiac expression of endothelin-1 mRNA in ischemic heart failure in rats

Objectives: Plasma endothelin (ET) concentrations are increased in heart failure. The aims of the present study were to investigate to what extent cardiac ET mRNA expression is induced in ischemic heart failure and whether there may be compensatory downregulation of myocardial mRNA levels for the ET(A) and ET(B) receptor subtypes. Methods: In rats with ischemic heart failure (left ventricular end-diastolic pressure > 15 mmHg) due to left coronary artery ligation, Northern blot analyses were performed on mRNA isolated from cardiac tissues. Results: A substantial upregulation was revealed in all chambers of the failing hearts. Up to 27-fold upregulation (mean 10.6 +/- 4.0, P = 0.002) of left ventricular ET-1 mRNA levels was measured 1 week after myocardial infarction, whereas only a modest upregulation was detected after 6 weeks (mean 2.7 +/- 0.5, P < 0.05). Ribonuclease protection assay revealed 2.8 +/- 0.4-fold higher levels of ET-1 mRNA in the left ventricular area subjected to myocardial infarction compared to the non-infarcted tissue after 1 week. Left ventricular ET-1 mRNA correlated significantly with left ventricular end-diastolic pressure after 1 week (r(2) = 0.86, P = 0.007). The ET(A) and ET(B) receptor mRNA levels tended to increase 1 week after myocardial infarction although these changes were not statistically significant. Conclusions: Cardiac ET-1 mRNA levels are increased in ischemic heart failure and correlate significantly with left ventricular end-diastolic pressure 1 week after myocardial infarction. The increase in cardiac ET-1 mRNA is not accompanied by a decrease in ET receptor mRNA.