Beta-endorphin and central control of arterial blood pressure during challenge of circulatory homeostasis.
A variety of neurotransmitters and neuropeptides appear to participate in the central control mechanisms of arterial blood pressure. Our knowledge of these mechanisms is limited as yet. In the present study the involvement of the opioid peptide beta-endorphin in circulatory homeostasis was studied. Under conditions in which beta-endorphin does not affect basal blood pressure and heart rate this peptide had a pronounced prohypotensive influence in normotensive rats. This was found for two conditions during which circulatory homeostasis was challenged. Firstly, during blood letting in a rat model employed to test blood pressure regulation during hemorrhage, and secondly, for the central hypotensive action of alpha-methyldopa. In the first model hypotension was produced by stepwise bleeding to respectively 80, 60 and 40 mmHg mean arterial pressure. Intracerebroventricular (i.c.v.) administration of an antiserum raised against beta-endorphin or of naloxone (s.c. or i.c.v.) caused a significant increase in the required bleeding volume, whereas an opposite action was observed after the injection of morphine (s.c.) or of beta-endorphin (i.c.v.). The role of beta-endorphin in the hypotensive action of alpha-methyldopa, given intracisternally (i.c.) was evaluated in conscious rats equipped with chronic cannulas. Pretreatment with the opiate antagonist naltrexone (i.c.) caused an inhibition of the hypotension and bradycardia induced by alpha-methyldopa. This effect of the receptor antagonist was mimicked by i.c. administration of a beta-endorphin antiserum. Taken together, these data point to a hypotensive influence exerted by endogenous beta-endorphin under conditions during which circulatory homeostasis are challenged.
de Jong
W
W
Rudolf Magnus Institute for Pharmacology, State University of Utrecht, The Netherlands.
Sandor
P
P
Cox-van Put
J
J
van den Berg
M H
MH
van Giersbergen
P L
PL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001810:Blood Volume / Q000187:drug effects; D001815:Bloodletting; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000037:antagonists & inhibitors; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D008750:Methyldopa / Q000494:pharmacology; D009020:Morphine; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012769:Shock / Q000503:physiopathology*; D001615:beta-Endorphin / Q000502:physiology*
D004723:Endorphins; D009270:Naloxone; D008750:Methyldopa; D001615:beta-Endorphin; D009020:Morphine