ENDOTHELIN DOES NOT CONTRIBUTE TO THE ATTENUATION IN MYOCARDIAL-FUNCTION AND BLOOD-FLOW AFTER REPETITIVE ISCHEMIA IN THE RAT-HEART

An increased release of the potent vasoconstrictor endothelin (ET) may play a role in the development of myocardial stunning. We, therefore, hypothesized that blockade of ET with either monoclonal antibodies ag ainst ET-I and ET-3 (a-ET1/3-ab) or with the ETA receptor antagonist B Q123 would improve the reduction in myocardial blood flow (MBF; H-2 cl earance) and fractional wall thickening (FT; pulsed Doppler) after rep etitive ischemia/reperfusion in an in situ perfused rat model. Under b aseline conditions, ET-I dose dependently decreased MBF and increased mean arterial blood pessure. FT and heart rate were unaltered. Pretrea tment with both a-ET1/3-ab or BQ123 effectively blocked the effects of ET. Following repetitive ischemia, MBF was significantly reduced from 3.5 +/- 0.4 to 2.1 +/- 0.3 mi x min(-1), x g(-1) (p < 0.05) and FT fr om 16.2 +/- 1.7 to 9.4 +/- 1.1% in the control group (p < 0.05). Pretr eatment with either antibodies did not significantly improve the atten uation in MBF and FT at the end of the ischemic protocol. These result s indicate that inhibition of ET-I by monoclonal antibodies or by ETA receptor blockade does not influence the decrease in MBF and FT in rep etitive ischemia/reperfusion. We, therefore, propose that ET is not a major determinant in the development of myocardial stunning.