Endogenous kappa opioids mediate the action of brain angiotensin II to increase blood pressure.
The objectives of this study were to determine whether endogenous opioids are operative in modulating the CNS action of angiotensin II (ang II) on blood pressure and to determine whether this is mediated by endogenous mu or kappa opioid receptor agonists. The study design was: unanesthetized Wistar rats, 300-400g, previously instrumented with a cannula in the lateral cerebral ventricle and a catheter in the femoral artery, had ang II, 0.5microg, injected into the lateral cerebral ventricle (ICV). Groups were allocated to receive naloxone, a mu opioid receptor antagonist or MR 2266 a selective kappa opioid receptor antagonist prior to ang II. In other experiments in unanesthetized rats, baroreceptor reflex function was assessed by intravenous injection of phenylephrine or nitroprusside and the interaction of endogenous opioids and ang II ascertained with use of the mu or kappa opioid receptor antagonist .


RESULTS
Ang II significantly (p<0.05) increased systolic and diastolic blood pressure. The kappa opioid antagonist, MR 2266, 25microg/kg ICV, significantly (p<0.05) reduced and MR 2266, 50microg/kg ICV, completely prevented the increase in blood pressure produced by ang II. In contrast, the mu opioid receptor antagonist, naloxone, 50microg/kg, ICV, did not significantly attenuate the blood pressure responses to ang II. Ang II induced alteration in baroreceptor function. The effect of ang II on baroreceptor function was significantly antagonized by the kappa opioid receptor antagonist MR 2266. In conclusion, these data indicate that: (a) endogenous opioids modulate the pressor response to intracerebral ang II, (b) this effect is mediated mainly through endogenous kappa opioid agonists and kappa rather than mu opioid receptors, (c) alteration of baroreceptor sensitivity by ang II is modulated by endogenous kappa opioids.
Rabkin
Simon W
SW
University of British Columbia, 9th Floor 2775 Laurel St.,Vancouver, BC, Canada V5Z 1M9. rabkin@interchange.ubc.ca
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure; D001923:Brain Chemistry / Q000502:physiology*; D004399:Dynorphins / Q000502:physiology*; D018847:Opioid Peptides / Q000502:physiology; D011311:Pressoreceptors / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D014661:Vasoconstriction
D018847:Opioid Peptides; D017473:Receptors, Opioid, kappa; D000804:Angiotensin II; D004399:Dynorphins