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Role of sensory neuron in reduction of endotoxin-induced hypotension in rats.
Crit Care Med. 2005 Apr; 33(4):847-54.CC

Abstract

OBJECTIVE

We attempted to determine whether activation of the sensory neuron contributes to reduction of endotoxin-induced hypotension by inhibiting tumor necrosis factor (TNF)-alpha production via calcitonin gene-related peptide (CGRP) release in rats.

DESIGN

Prospective, randomized, controlled study.

SETTING

Research laboratory at a university medical center.

SUBJECTS

Wistar rats weighing 220-280 g.

INTERVENTIONS

Mean arterial blood pressure was measured in rats administered endotoxin intravenously. Animals were pretreated with capsazepine (a vanilloid receptor antagonist), CGRP(8-37) (a CGRP receptor antagonist), and indomethacin before endotoxin administration. Levels of CGRP, 6-keto-prostaglandin F1alpha, TNF-alpha, and cytokine-induced neutrophil chemoattractant (CINC) were measured by enzyme immunoassay methods. The concentration of NO2/NO3 was measured using the Griess reagent. Tissue levels of messenger RNA of the inducible form of nitric oxide synthase (iNOS) and TNF-alpha were determined by reverse transcription polymerase chain reaction.

MEASUREMENTS AND MAIN RESULTS

Both lung levels of CGRP and plasma levels of 6-keto-prostaglandin F1alpha were increased after intravenous administration of endotoxin (5 mg/kg), peaking at 90 mins after endotoxin administration. Increases in plasma levels of 6-keto-prostaglandin F1alpha at 90 mins after endotoxin administration (766 +/- 134 pg/mL) were inhibited by pretreatment with capsazepine (373 +/- 44 pg/mL, p < .05), CGRP(8-37) (406 +/- 64 pg/mL, p < .05), and indomethacin (154 +/- 40 pg/mL, p < .05). Although none of the pretreatments affected a series of endotoxin-induced responses, including increases in lung tissue levels of TNF-alpha, CINC, and iNOS and the resultant hypotension in animals given 5 mg/kg endotoxin, such pretreatments enhanced these pathologic responses in animals given a smaller dose of endotoxin (1 mg/kg) to the same extent as those induced by 5 mg/kg of endotoxin, suggesting that shock responses induced by 5 mg/kg endotoxin are maximum responses and activation of sensory neurons in endotoxin-treated rats is essentially a reparative response.

CONCLUSION

Activation of sensory neurons might contribute to reduction of endotoxin-induced hypotension by releasing CGRP, which is capable of promoting endothelial production of prostacyclin.

Authors+Show Affiliations

Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15818115

Citation

Okajima, Kenji, et al. "Role of Sensory Neuron in Reduction of Endotoxin-induced Hypotension in Rats." Critical Care Medicine, vol. 33, no. 4, 2005, pp. 847-54.
Okajima K, Isobe H, Uchiba M, et al. Role of sensory neuron in reduction of endotoxin-induced hypotension in rats. Crit Care Med. 2005;33(4):847-54.
Okajima, K., Isobe, H., Uchiba, M., & Harada, N. (2005). Role of sensory neuron in reduction of endotoxin-induced hypotension in rats. Critical Care Medicine, 33(4), 847-54.
Okajima K, et al. Role of Sensory Neuron in Reduction of Endotoxin-induced Hypotension in Rats. Crit Care Med. 2005;33(4):847-54. PubMed PMID: 15818115.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of sensory neuron in reduction of endotoxin-induced hypotension in rats. AU - Okajima,Kenji, AU - Isobe,Hirotaka, AU - Uchiba,Mitsuhiro, AU - Harada,Naoaki, PY - 2005/4/9/pubmed PY - 2005/5/11/medline PY - 2005/4/9/entrez SP - 847 EP - 54 JF - Critical care medicine JO - Crit Care Med VL - 33 IS - 4 N2 - OBJECTIVE: We attempted to determine whether activation of the sensory neuron contributes to reduction of endotoxin-induced hypotension by inhibiting tumor necrosis factor (TNF)-alpha production via calcitonin gene-related peptide (CGRP) release in rats. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory at a university medical center. SUBJECTS: Wistar rats weighing 220-280 g. INTERVENTIONS: Mean arterial blood pressure was measured in rats administered endotoxin intravenously. Animals were pretreated with capsazepine (a vanilloid receptor antagonist), CGRP(8-37) (a CGRP receptor antagonist), and indomethacin before endotoxin administration. Levels of CGRP, 6-keto-prostaglandin F1alpha, TNF-alpha, and cytokine-induced neutrophil chemoattractant (CINC) were measured by enzyme immunoassay methods. The concentration of NO2/NO3 was measured using the Griess reagent. Tissue levels of messenger RNA of the inducible form of nitric oxide synthase (iNOS) and TNF-alpha were determined by reverse transcription polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Both lung levels of CGRP and plasma levels of 6-keto-prostaglandin F1alpha were increased after intravenous administration of endotoxin (5 mg/kg), peaking at 90 mins after endotoxin administration. Increases in plasma levels of 6-keto-prostaglandin F1alpha at 90 mins after endotoxin administration (766 +/- 134 pg/mL) were inhibited by pretreatment with capsazepine (373 +/- 44 pg/mL, p < .05), CGRP(8-37) (406 +/- 64 pg/mL, p < .05), and indomethacin (154 +/- 40 pg/mL, p < .05). Although none of the pretreatments affected a series of endotoxin-induced responses, including increases in lung tissue levels of TNF-alpha, CINC, and iNOS and the resultant hypotension in animals given 5 mg/kg endotoxin, such pretreatments enhanced these pathologic responses in animals given a smaller dose of endotoxin (1 mg/kg) to the same extent as those induced by 5 mg/kg of endotoxin, suggesting that shock responses induced by 5 mg/kg endotoxin are maximum responses and activation of sensory neurons in endotoxin-treated rats is essentially a reparative response. CONCLUSION: Activation of sensory neurons might contribute to reduction of endotoxin-induced hypotension by releasing CGRP, which is capable of promoting endothelial production of prostacyclin. SN - 0090-3493 UR - https://www.unboundmedicine.com/medline/citation/15818115/Role_of_sensory_neuron_in_reduction_of_endotoxin_induced_hypotension_in_rats_ L2 - https://dx.doi.org/10.1097/01.ccm.0000159721.72629.49 DB - PRIME DP - Unbound Medicine ER -