Detrimental effect of endothelin-1 on regional myocardial energy metabolism in underperfused diabetic rat hearts

• Published in: Japanese Journal of Pharmacology 1999, Vol.79 (suppl.1), p.174-174
• Main Authors: Higuchi, Makie, Miyagi, Kanako, Ameho, Clement K, Sakanashi, Matao
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)34708-0

A pathophysiological role of endothelin in ischemic myocardial injury has been proposed. In the diabetic rats, changes in the cardiovascular responsiveness to endothelin-1 (ET-1) were reported. In the present study, we examined the effect of ET-1 on the left ventricular (LV) dysfunction during underperfusion in isolated paced isovolumetric 6-week diabetic rat hearts without or with BQ-123. Agents were infused for 15-20 min before as well as during 60-min underperfusion. Results： ET-1 increased the coronary perfusion pressure and LV contractility during normal perfusion and during underperfusion. A moderate increase in LV stiffness during underperfusion was slightly enhanced by ET-1. The increases were reduced by BQ 123, except of CPP during normal perfusion. At 60-min underperfusion, tissue ATP, creatine phosphate (CP) and CP/inorganic phosphate (Pi) ratio decreased, and Pi and lactate increased, particularly in the LV subendocardium. ET-1 enhanced the abnormal myocardial energy metabolism, particularly in the subepicardium. The changes were reduced by BQ 123. Conclusions： ET-1 may have harmful effects in underperfused diabetic hearts, particularly in the LV subepicardium. The ET-1 induced detrimental effects in the ischemic diabetic heart are prevented by BQ 123, a selective ET_A receptor antagonist.