Differential effects of endothelin-1 on normal and postischemic reperfused myocardium.
Using an isolated rat heart preparation and 31P magnetic resonance spectroscopy, we studied the effects of endothelin-1 (ET-1) and U-46619, a thromboxane-A2 analogue, on coronary flow (CF), left ventricular developed pressure (LVP), and high-energy phosphate metabolism under control conditions (normal myocardium) and during postischemic reperfusion (reperfused myocardium). The selected doses of ET-1 and U-46619 reduced CF in the normal myocardium to a similar extent (47.8 +/- 1.5% and 48.7 +/- 4.6%, respectively). In contrast to ET-1, U-46619 induced a depression of LVP (20.2 +/- 6.9% versus 6.8 +/- 4.7%; p < 0.05) which was accompanied by an intracellular acidosis, indicating that a low-flow ischemia occurred. In reperfused hearts, the ET-1-induced decrease in CF was more pronounced compared to U-46619 (79.5 +/- 1.6% versus 59.0 +/- 5.9%; p < 0.05) and to ET-1-induced decrease in CF in the normal myocardium (74.0 +/- 7.9% versus 32.4 +/- 6.3%; p < 0.05). This was accompanied by a large decrease in LVP and in levels of high-energy phosphate compounds. Therefore, the effects of ET-1 but not of U-46619 are enhanced in reperfused hearts. This may contribute to the delayed recovery of the postischemic reperfused myocardium.
Zaugg
C E
CE
Department of Medicine, University Hospitals, Basel, Switzerland.
Zhu
P
P
Simper
D
D
Lüscher
T F
TF
Allegrini
P R
PR
Buser
P T
PT
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
D016232:Endothelins; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate