Central opioid receptors and baroreflex control of sympathetic and cardiovascular function.
The effect of central opioid receptor activation and blockade on arterial baroreflex regulation of cardiovascular function was studied. Baroreceptor reflexes were elicited in urethane-anesthetized rats by graded electrical stimulation of the aortic nerve while mean arterial pressure, heart rate and sympathetic nerve activity were recorded simultaneously. Baroreflex response curves were constructed after intracisternal administration of saline vehicle, after intracisternal infusion of the relatively selective mu and delta opioid receptor agonists D-Ala2-MePhe4-Gly(ol)5 enkephalin (DAGO), or D-Ala2-D-Leu5 enkephalin (DADLE) respectively, and again after i.v. naloxone. Reflex reductions in mean arterial pressure, heart rate and sympathetic nerve activity elicited by aortic nerve stimulation were attenuated in a dose-related fashion by intracisternal DAGO. Opioid effects were greatest at low levels of baroreceptor activation and became progressively less marked as the frequency of aortic nerve stimulation was increased. Baroreflex impairment was reversed completely by i.v. naloxone. Centrally administered DADLE also attenuated baroreceptor reflexes, but was approximately 10- to 100-fold less potent than an equimolar amount of DAGO. The effect of DADLE was reversed by a lower dose of naloxone than was required to normalize baroreflexes after DAGO. These results suggest that the effect of DADLE on baroreflexes was mediated by activation of mu rather than delta opioid receptors. No evidence was obtained to suggest a role for endogenous opioid modulation of baroreflexes because i.v. naloxone was without effect. These results demonstrate that activation of central mu opioid receptors significantly impairs baroreflex control of sympathetic and cardiovascular function.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; 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; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D011311:Pressoreceptors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D012018:Reflex / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000502:physiology*
D004745:Enkephalins; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine