At. Omoniyi et al., A peripheral site of action for the attenuation of baroreflex-mediated bradycardia by intravenous mu-opioid agonists, J CARDIO PH, 35(2), 2000, pp. 269-274
Citations number
35
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
We previously reported that i.v. DAMGO (Tyr-D-Ala-Gly-NMePhe-Gly-ol), a sel
ective mu-opioid agonist, causes an increase in blood pressure with no chan
ge in heart rate in unanesthetized sheep and subsequently demonstrated that
DAMGO attenuates baroreflex-mediated bradycardia. To determine the site an
d mechanism by which mu-agonists inhibit baroreflex sensitivity, we have ca
rried out further investigations by using DAMGO and another mu-agonist, DAL
DA (Tyr-D-Arg-Phe-Lys-NH2). The bradycardic response to norepinephrine (NE)
was significantly blunted after i.v. DAMGO or DALDA in both nonpregnant an
d pregnant sheep. In contrast, the tachycardic response to sodium nitroprus
side (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 quaternar
y opioid antagonist, naloxone methiodide (NM), completely blocked the atten
uation of baroreflex sensitivity by DAMGO and DALDA in both nonpregnant and
pregnant animals. These data suggest that in addition to central mechanism
s, mu-opioid agonists can inhibit baroreflex sensitivity at a peripheral si
te, most likely by inhibiting vagal influence on heart-rate control rather
than by acting directly at baroreceptors.