The pressor response to central administration of beta-endorphin results from a centrally mediated increase in noradrenaline release and adrenaline secretion.
1. The effects of intracerebroventricular (i.c.v.) and intracisternal (i.c.) administration of beta-endorphin (0.01, 0.1 and 1.0 nmol kg-1) were examined in conscious rabbits. 2. After i.c.v. beta-endorphin, mean arterial pressure (MAP) increased, heart rate (HR) fell, plasma noradrenaline, adrenaline and glucose increased and there was a rise in PaCO2 and fall in PaO2; these effects were reversed by intravenous (i.v.) naloxone (300 nmol kg-1). 3. A combination of prazosin (2 mg kg-1) and yohimbine (1 mg kg-1), given i.v., prevented the rise in MAP induced by i.c.v. beta-endorphin. 4. After i.c. beta-endorphin, MAP, HR and plasma catecholamines were not significantly altered but there was a similar degree of respiratory depression. 5. Clonidine (1.0 micrograms kg-1, i.c.) reduced MAP and HR; these effects were not blocked by i.v. naloxone (6 mumol kg-1). 6. These results demonstrate that beta-endorphin acts centrally, probably mainly on periventricular mu-opioid receptors, to increase adrenaline secretion and sympathetic nerve activity leading to alpha-adrenoceptor-mediated vasoconstriction. The respiratory depression is probably mediated by brainstem mu-receptors. 7. A role for beta-endorphin in the central hypotensive action of alpha 2-adrenoceptor agonists was opposed by finding that opioid receptor antagonism with naloxone did not block the effects of clonidine.
May
C N
CN
Medical Unit, St. Mary's Hospital Medical School, London.
Whitehead
C J
CJ
Mathias
C J
CJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D001615:beta-Endorphin / Q000494:pharmacology*
D004745:Enkephalins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D001615:beta-Endorphin; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine