Effects of endothelin on isolated ischaemic rat hearts during ramiprilat, bradykinin and indomethacin perfusion.
In isolated ischaemic rat hearts, endothelin induced a short transient increase, followed by a lasting decrease in coronary flow and an increase in the left ventricular dp/dt max in a concentration-dependent manner. Both enzyme activities and lactate output were increased in the venous effluent. Myocardial tissue levels of glycogen, ATP and creatine phosphate were reduced. Endothelin aggravated post-ischaemic reperfusion arrhythmias. Perfusion with ramiprilat and bradykinin increased coronary flow and left ventricular dp/dt max and reduced reperfusion arrhythmias; enzyme activities and lactate output were significantly reduced and in the myocardial tissue glycogen and energy-rich phosphates were preserved. In comparison, indomethacin prolonged reperfusion arrhythmias, decreased coronary flow and increased the enzyme activities with no changes in myocardial metabolism. When ramiprilat and bradykinin were combined with endothelin, reperfusion arrhythmias and the enzyme activities were reduced but the decrease in coronary flow could not be fully blocked. Indomethacin aggravated the endothelin-induced coronary flow reduction, enzyme release and reperfusion arrhythmias but had no effects on the other parameters.
Linz
W
W
Hoechst AG, Frankfurt/Main, Federal Republic of Germany.
Albus
U
U
Schölkens
B A
BA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001920:Bradykinin / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D010455:Peptides / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D017257:Ramipril / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D016232:Endothelins; D010455:Peptides; D011758:Pyrroles; D014662:Vasoconstrictor Agents; C052549:ramiprilat; D017257:Ramipril; D001920:Bradykinin; D007213:Indomethacin