24 September 2008
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 against ET-1 and ET-3 (a-ETl/3-ab) or with the ET<sub>a</sub> receptor antagonist BQ123 would improve the reduction in myocardial blood flow (MBF; H<sub>2</sub> clearance) and fractional wall thickening (FT; pulsed Doppler) after repetitive ischemia/reperfusion in an in situ perfused rat model. Under baseline conditions, ET-1 dose dependently decreased MBF and increased mean arterial blood pessure. FT and heart rate were unaltered. Pretreatment with both a-ETl/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 ml × min<sup>–1</sup> × g<sup>–1</sup> (p& < 0.05) and FT from 16.2 ± 1.7 to 9.4 ± 1.1% in the control group (p& < 0.05). Pretreatment with either antibodies did not significantly improve the attenuation in MBF and FT at the end of the ischemic protocol. These results indicate that inhibition of ET-1 by monoclonal antibodies or by ET<sub>A</sub> receptor blockade does not influence the decrease in MBF and FT in repetitive ischemia/reperfusion. We, therefore, propose that ET is not a major determinant in the development of myocardial stunning.