DIFFERENTIAL-EFFECTS OF ENDOTHELIN-1 ON NORMAL AND POSTISCHEMIC REPERFUSED MYOCARDIUM

Using an isolated rat heart preparation and P-31 magnetic resonance sp ectroscopy, we studied the effects of endothelin-I (ET-1) and U-46619, a thromboxane-A2 analogue, on coronary flow (CF), left ventricular de veloped pressure (LVP), and high-energy phosphate metabolism under con trol conditions (normal myocardium) and during postischemic reperfusio n (reperfused myocardium). The selected doses of ET-I and U-46619 redu ced CF in the normal myocardium to a similar extent (47.8 +/- 1.5% and 48.7 +/- 4.6%, respectively). In contrast to ET-1, U-46619 induced a depression of LVP (20.2 +/- 6.9% versus 6.8 +/- 4.7%; p<0.05) which wa s accompanied by an intracellular acidosis, indicating that a low-flow ischemia occurred. In reperfused hearts, the ET-1-induced decrease in CF was more pronounced compared to U-46619 (79.5 +/- 1.6% versus 59.0 +/- 5.9%; p<0.05) and to ET-1-induced decrease in CF in the normal my ocardium (74.0 +/- 7.9% versus 32.4 +/- 6.3%; p<0.05). This was accomp anied by a large decrease in LVP and in levels of high-energy phosphat e compounds. Therefore, the effects of ET-1 but not of U-46619 are enh anced in reperfused hearts. This may contribute to the delayed recover y of the postischemic reperfused myocardium.