Cardiovascular and respiratory effects of mu-, delta- and kappa-opiate agonists microinjected into the anterior hypothalamic brain area of awake rats.
Relatively selective mu-, delta- and kappa-opiate agonists were microinjected into anterior hypothalamic and septal brain regions of the unanesthetized rat in order to investigate the potential role of specific opiate receptors in central cardiovascular regulation. Low doses (0.2-3 nmol) of both [D-Ala2,MePhe4,Gly-(ol)5] enkephalin (DAGO, mu-agonist) and [D-Ala2,D-Leu5]enkephalin (DADL, delta-agonist) caused dose-dependent increases in blood pressure and heart rate which were naloxone reversible. Higher doses (7.5-30 nmol) of DAGO and DADL produced pressor responses but had little effect on heart rate. The kappa-agonist MR 2034 had no effect on cardiovascular parameters at these doses. DAGO but not MR 2034 also depressed respiration at the higher doses resulting in hypoxia, hypercapnia and acidosis while DADL only slightly depressed respiration. DAGO was approximately 10-fold more potent than DADL in eliciting cardiovascular and respiratory responses. These findings implicate mu-receptors in mediating the cardiovascular and respiratory effects of opiates at anterior hypothalamic sites.
D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; 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*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D009019:Morphinans / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D012119:Respiration / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects
D001575:Benzomorphans; D004745:Enkephalins; D009019:Morphinans; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C032478:MR 2034; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine