Delta and Mu receptor agonists correlate with greater depression of cardiac function than morphine sulfate in perfused rat hearts.
In previous studies done in our laboratory, we demonstrated that morphine sulfate could depress heart rate and cardiac output when added to the perfusate of a working rat heart model using a modified Langendorff preparation. In this study we investigated three different delta agonists and a mu agonist by adding each to the perfusate in a fashion similar to the experiments done with morphine sulfate. We found that all three delta agonists, leu-enkephalin, D-ala-D-leu-enkephalin (DADL), and D-Pen enkephalin, would significantly decrease cardiac output. In the case of D-Pen enkephalin, heart rate and stroke volume were also significantly decreased. Additionally the mu agonist Tyr-D-ala-gly-N-met-phe-gly-ol (DAGO) also caused a significant decrease in heart rate, cardiac output, and stroke volume. The data suggest that all three delta agonists and DAGO are capable of depressing heart rate, cardiac output, and stroke volume at concentrations between 10(3) and 10(4) lower than those used in studies with morphine sulfate.
Vargish
T
T
Department of Surgery, University of Chicago, Illinois 60637.
Beamer
K C
KC
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D013318:Stroke Volume / Q000187:drug effects
D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine