title: Endothelin does not contribute to the attenuation in myocardial function and blood flow after repetitive ischemia in the rat heart.
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-ET1/3-ab) or with the ET(A) receptor antagonist BQ123 would improve the reduction in myocardial blood flow (MBF; H2 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 pressure. FT and heart rate were unaltered. Pretreatment 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 ml x min-1 x g-1 (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(A) 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.
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany. ctiefenbacher@krzmail.krz.uni-heidelberg.de
authors.forename: C P
authors.initials: CP
authors.lastname: Tiefenbacher
authors.forename: A
authors.initials: A
authors.lastname: Tweddell
authors.forename: S
authors.initials: S
authors.lastname: Batkai
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.forename: H
authors.initials: H
authors.lastname: Tillmanns
authors.forename: W
authors.initials: W
authors.lastname: Kübler
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D011920:Rats, Inbred WF; D044022:Receptor, Endothelin A; D012008:Recurrence
chemical_list: D000911:Antibodies, Monoclonal; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; C072247:cyclo(Trp-Asp-Pro-Val-Leu)