Key result
IV mu-opioid agonists blunt norepinephrine-induced bradycardia in sheep, blocked by peripheral opioid antagonism.
Why the study?
Do intravenous mu-opioid agonists attenuate baroreflex-mediated bradycardia at a peripheral site in unanesthetized sheep?
Do intravenous mu-opioid agonists attenuate baroreflex-mediated bradycardia at a peripheral site in unanesthetized sheep?
Mu-opioid agonists can inhibit baroreflex sensitivity at a peripheral site, likely by inhibiting vagal influence on heart-rate control.
Hypothesis-generating for peripheral mu-opioid blunting of baroreflex bradycardia; human studies needed before any clinical inference.
We previously reported that i.v. DAMGO (Tyr-D-Ala-Gly-NMePhe-Gly-ol), a selective mu-opioid agonist, causes an increase in blood pressure with no change in heart rate in unanesthetized sheep and subsequently demonstrated that DAMGO attenuates baroreflex-mediated bradycardia. To determine the site and mechanism by which mu-agonists inhibit baroreflex sensitivity, we have carried out further investigations by using DAMGO and another mu-agonist, DALDA (Tyr-D-Arg-Phe-Lys-NH2). The bradycardic response to norepinephrine (NE) was significantly blunted after i.v. DAMGO or DALDA in both nonpregnant and pregnant sheep. In contrast, the tachycardic response to sodium nitroprusside (SNP) remained unchanged in the presence of DAMGO or DALDA. In view of the highly restricted distribution of DALDA across the blood-brain barrier (BBB), we hypothesized that the blunting of reflex-mediated bradycardia by mu-opioid agonists can occur peripherally. Pretreatment with the quaternary opioid antagonist, naloxone methiodide (NM), completely blocked the attenuation of baroreflex sensitivity by DAMGO and DALDA in both nonpregnant and pregnant animals. These data suggest that in addition to central mechanisms, mu-opioid agonists can inhibit baroreflex sensitivity at a peripheral site, most likely by inhibiting vagal influence on heart-rate control rather than by acting directly at baroreceptors.
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Omoniyi et al. (2000) studied this question. Intravenous mu-opioid agonists (DAMGO and DALDA) was evaluated on Bradycardic response to norepinephrine. Intravenous mu-opioid agonists (DAMGO and DALDA) significantly blunted the bradycardic response to norepinephrine in sheep, an effect completely blocked by peripheral opioid antagonism.
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