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      Endothelin Does Not Contribute to the Attenuation in Myocardial Function and Blood Flow after Repetitive Ischemia in the Rat Heart

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          Abstract

          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.

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          Author and article information

          Journal
          JVR
          J Vasc Res
          10.1159/issn.1018-1172
          Journal of Vascular Research
          S. Karger AG
          1018-1172
          1423-0135
          1997
          1997
          24 September 2008
          : 34
          : 6
          : 447-454
          Affiliations
          aDepartment of Cardiology, University of Heidelberg, Germany; bDepartment of Cardiology, University of Glasgow, UK
          Article
          159255 J Vasc Res 1997;34:447–454
          10.1159/000159255
          9425997
          © 1997 S. Karger AG, Basel

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          Page count
          Pages: 8
          Categories
          Research Paper

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