Activation of glucocorticoid receptors and the effect of naloxone during hemorrhagic hypotension.
Evidence indicates that endogenous opioid peptides and glucocorticoids participate in the control of cardiovascular regulation during hemorrhagic shock. In the present study, we investigated a possible interaction between brain opioid peptides and adrenal corticosteroids regarding the control of arterial pressure during hemorrhage. The bleeding volumes required to lower arterial pressure to 80, 60 and 40 mmHg were studied in anesthetized sham-operated (SHAM) and adrenalectomized (ADX) rats. I.c.v. administration of 10 micrograms of naloxone resulted in a significant increase in the bleeding volume required to lower arterial pressure from 60 to 40 mmHg in SHAM animals, whereas no effect of naloxone was observed in ADX animals. Replacement therapy with a 100% corticosterone pellet (100 mg, s.c.), but not with a 12.5% corticosterone pellet (12.5 mg corticosterone and 87.5 mg cholesterol, s.c.), resulted in an effect of naloxone on the bleeding volume in ADX animals. The effect of replacement therapy could be inhibited by i.c.v. pretreatment with the synthetic glucocorticoid receptor antagonist, RU38486 (100 ng). These data suggest that (1) opioid mechanisms are involved in the regulation of blood pressure during hemorrhage, and (2) occupancy of glucocorticoid receptors is required for naloxone to exert its hemodynamic effect during hemorrhagic hypotension in ADX rats.
Eijgelshoven
M H
MH
Rudolf Magnus Institute for Pharmacology, University of Utrecht, The Netherlands.
De Kloet
E R
ER
Van den Berg
D T
DT
Van Giersbergen
P L
PL
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000627:therapeutic use; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015735:Mifepristone / Q000627:therapeutic use*; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D012771:Shock, Hemorrhagic / Q000188:drug therapy*
D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D009270:Naloxone; D003345:Corticosterone