Endothelin-3-induced microvascular incompetence and mitochondrial damage in rat myocardium.

1. To determine the possible role of an endothelin in the development of postischaemic microvascular incompetence, isolated buffer-perfused rat hearts were perfused with endothelin-3 (ET-3) in phosphate buffer. 2. ET-3 produced a reduction in coronary flow rate, heart rate and arrhythmia. There was a marked reduction in the density of competent capillaries, and the myocytes showed vacuolation and mitochondrial damage in regions where microvascular incompetence was most severe. 3. These results indicate that ET-3 can substantially reduce microvascular perfusion in the heart and can also cause damage to the myocyte.