Dynorphin, naloxone, and overflow of norepinephrine during cardiac nerve stimulation in dogs.
The effects of dynorphin-(1-9) and naloxone on norepinephrine (NE) overflow and myocardial contractility were determined during left cardiac nerve stimulation in the anesthetized dog. Stimulation-induced increases in NE overflow from the left ventricle were monitored during control conditions, during infusion of dynorphin-(1-9), during dynorphin plus naloxone, and after naloxone alone. Four electrical stimulations were applied for 1 min at 20-min intervals. Repeated left cardiac nerve stimulations (control group) reduced stimulated NE overflow 50-60% by 1 h. If stimulations were only conducted at 0 and 1 h, the decline in NE overflow was not observed. Intracoronary dynorphin (2 nmol.min-1.kg-1, 20 min) lowered the stimulation-induced increase in NE overflow further and reduced first time derivative of left ventricular pressure (dP/dt) and myocardial O2 consumption responses. Naloxone (100 micrograms/kg) prevented all of the dynorphin-mediated effects. When given alone, naloxone increased both NE overflow and left ventricular dP/dt during stimulation and prevented or significantly delayed the gradual decline in overflow observed in stimulated controls. A postjunctional effect of dynorphin was evaluated by comparing contractile responses to the intracoronary infusion of NE before and during dynorphin. Dynorphin did not alter contractile function at rest or during NE infusion. In summary, dynorphin-(1-9) depresses nerve stimulation-induced, cardiac NE overflow, and myocardial contractility in a naloxone-reversible fashion. Alone, naloxone appears to regulate stimulated NE overflow through a qualitatively different mechanism. Endogenous opioids may normally moderate myocardial function during cardiac nerve stimulation by regulating junctional NE concentrations through a combination of effects on NE release and/or its subsequent reuptake.
Gu
H
H
Department of Physiology, Texas College of Osteopathic Medicine, Fort Worth 76107.
Barron
B A
BA
Gaugl
J F
JF
Caffrey
J L
JL
D000818:Animals; D004285:Dogs; D004399:Dynorphins / Q000494:pharmacology*; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011312:Pressure; D013564:Sympathetic Nervous System / Q000502:physiology*; D016277:Ventricular Function, Left
D010446:Peptide Fragments; D009270:Naloxone; D004399:Dynorphins; C040238:dynorphin A (1-9); D009638:Norepinephrine