Mechanisms involved in the rapid dissipation of plasma epinephrine response to bacterial endotoxin in conscious rats.
Conscious rats treated with bolus endotoxin (ET; 4.0 mg/kg) increased plasma epinephrine (Epi) 48-fold (from 134 +/- 5 to 6,545 +/- 1,607 pg/ml) at 30 min, but by 6 h this elevation was less than 9-fold above control (1,174 +/- 166 pg/ml). In contrast, plasma norepinephrine (NE) elevation (6.5-fold above control) was maintained during the protocol. The present study was designed to test the hypothesis that the decreased Epi response following ET was due to 1) depletion of adrenal Epi content such that adrenomedullary stimulation would not release Epi, 2) decreased Epi release with direct stimulation, i.e., desensitization of release, or 3) decreased afferent signals generated by ET itself. In these experiments an initial low ET dose (0.5 mg/kg) was followed 3 h later by a second dose of either the same (0.5 mg/kg) or greater (4.0 mg/kg) magnitude. Plasma Epi was elevated following the initial (low) dose but not following the same second (0.5 mg/kg) dose, whereas the second higher dose (4.0 mg/kg) resulted in elevated plasma Epi. This response to high dose was 60% less than that observed with 4.0 mg/kg as an initial dose. Just before the second ET bolus, there was no depletion of adrenal Epi content (P greater than 0.05 saline vs. ET treated), and direct nerve stimulation demonstrated enhanced rather than attenuated Epi release from the adrenal medulla (P less than 0.05 saline vs. ET treated). These results suggest that the decline in Epi following the ET-induced elevation may be mediated by a decrease in the afferent signal that initiates Epi release.
Qi
M
M
Department of Physiology, Loyola University Medical Center, Maywood, Illinois 60153.
Zhou
Z Z
ZZ
Wurster
R D
RD
Jones
S B
SB
D000311:Adrenal Glands / Q000294:innervation / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D004558:Electric Stimulation; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood* / Q000378:metabolism; D006339:Heart Rate; D007700:Kinetics; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D051381:Rats; D012475:Salmonella
D001786:Blood Glucose; D004731:Endotoxins; D007773:Lactates; D019344:Lactic Acid; D009638:Norepinephrine; D004837:Epinephrine