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Ischemia/reperfusion-induced increase in the hepatic level of prostacyclin is mainly mediated by activation of capsaicin-sensitive sensory neurons in rats.
J Lab Clin Med. 2002 Apr; 139(4):218-26.JL

Abstract

Capsaicin-sensitive sensory neurons are nociceptive neurons that release calcitonin gene-related peptide (CGRP) on activation by various noxious stimuli. CGRP has been shown to increase the endothelial production of prostacyclin, which reduces ischemia/reperfusion (I/R)-induced liver injury. Therefore, if the sensory neurons can be activated by the pathologic process of hepatic I/R, they might help ameliorate I/R-induced liver injury by promoting the endothelial production of prostacyclin, also known as prostaglandin I(2). In this study, we examined these possibilities using a rat model of I/R-induced liver injury. Male Wistar rats were subjected to 60-minute hepatic ischemia and subsequent reperfusion. Hepatic levels of 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), a stable metabolite of prostacyclin, were significantly increased after hepatic I/R, peaking 1 hour after reperfusion. Administration of capsaicin and CGRP significantly enhanced I/R-induced increases in hepatic levels of 6-keto-PGF(1alpha), increased hepatic-tissue blood flow after reperfusion, and inhibited the I/R-induced increase in tissue levels of both tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase. Capsazepine, a vanilloid receptor antagonist; CGRP(8-37), a CGRP-receptor antagonist; l-nitro-arginine-methyl-ester (L-NAME), a nonselective inhibitor of nitric oxide (NO) synthase (NOS); and indomethacin, a nonselective inhibitor of cyclooxygenase, inhibited the I/R-induced increases in hepatic tissue levels of 6-keto-PGF(1alpha) and decreased hepatic-tissue blood flow after reperfusion. These compounds significantly enhanced the I/R-induced increases in hepatic tissue levels of both TNF-alpha and myeloperoxidase. Although I/R-induced liver injury was significantly reduced by capsaicin and CGRP, it was exacerbated by capsazepine, CGRP(8-37), L-NAME, and indomethacin. Administration of aminoguanidine, a selective inhibitor of the inducible form of NOS, and NS-398, a selective inhibitor of cyclooxygenase-2, demonstrated no effects on the liver injury or the hepatic levels of 6-keto-PGF(1alpha). These findings strongly suggest that the activation of the sensory neurons helps ameliorate I/R-induced liver injury both by increasing hepatic-tissue blood flow and by limiting inflammatory response through the enhancement of endothelial production of prostacyclin. In the sensory neuron-mediated enhancement of endothelial production of prostacyclin, CGRP-induced activation of both endothelial NOS and cyclooxygenase-1 may be critically involved.

Authors+Show Affiliations

Department of Laboratory Medicine, Kumamoto University School of Medicine, Honjo 1-1-1, Kumamoto 068-0811, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12024109

Citation

Harada, Naoaki, et al. "Ischemia/reperfusion-induced Increase in the Hepatic Level of Prostacyclin Is Mainly Mediated By Activation of Capsaicin-sensitive Sensory Neurons in Rats." The Journal of Laboratory and Clinical Medicine, vol. 139, no. 4, 2002, pp. 218-26.
Harada N, Okajima K, Uchiba M, et al. Ischemia/reperfusion-induced increase in the hepatic level of prostacyclin is mainly mediated by activation of capsaicin-sensitive sensory neurons in rats. J Lab Clin Med. 2002;139(4):218-26.
Harada, N., Okajima, K., Uchiba, M., & Katsuragi, T. (2002). Ischemia/reperfusion-induced increase in the hepatic level of prostacyclin is mainly mediated by activation of capsaicin-sensitive sensory neurons in rats. The Journal of Laboratory and Clinical Medicine, 139(4), 218-26.
Harada N, et al. Ischemia/reperfusion-induced Increase in the Hepatic Level of Prostacyclin Is Mainly Mediated By Activation of Capsaicin-sensitive Sensory Neurons in Rats. J Lab Clin Med. 2002;139(4):218-26. PubMed PMID: 12024109.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ischemia/reperfusion-induced increase in the hepatic level of prostacyclin is mainly mediated by activation of capsaicin-sensitive sensory neurons in rats. AU - Harada,Naoaki, AU - Okajima,Kenji, AU - Uchiba,Mitsuhiro, AU - Katsuragi,Takeshi, PY - 2002/5/25/pubmed PY - 2002/6/21/medline PY - 2002/5/25/entrez SP - 218 EP - 26 JF - The Journal of laboratory and clinical medicine JO - J Lab Clin Med VL - 139 IS - 4 N2 - Capsaicin-sensitive sensory neurons are nociceptive neurons that release calcitonin gene-related peptide (CGRP) on activation by various noxious stimuli. CGRP has been shown to increase the endothelial production of prostacyclin, which reduces ischemia/reperfusion (I/R)-induced liver injury. Therefore, if the sensory neurons can be activated by the pathologic process of hepatic I/R, they might help ameliorate I/R-induced liver injury by promoting the endothelial production of prostacyclin, also known as prostaglandin I(2). In this study, we examined these possibilities using a rat model of I/R-induced liver injury. Male Wistar rats were subjected to 60-minute hepatic ischemia and subsequent reperfusion. Hepatic levels of 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), a stable metabolite of prostacyclin, were significantly increased after hepatic I/R, peaking 1 hour after reperfusion. Administration of capsaicin and CGRP significantly enhanced I/R-induced increases in hepatic levels of 6-keto-PGF(1alpha), increased hepatic-tissue blood flow after reperfusion, and inhibited the I/R-induced increase in tissue levels of both tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase. Capsazepine, a vanilloid receptor antagonist; CGRP(8-37), a CGRP-receptor antagonist; l-nitro-arginine-methyl-ester (L-NAME), a nonselective inhibitor of nitric oxide (NO) synthase (NOS); and indomethacin, a nonselective inhibitor of cyclooxygenase, inhibited the I/R-induced increases in hepatic tissue levels of 6-keto-PGF(1alpha) and decreased hepatic-tissue blood flow after reperfusion. These compounds significantly enhanced the I/R-induced increases in hepatic tissue levels of both TNF-alpha and myeloperoxidase. Although I/R-induced liver injury was significantly reduced by capsaicin and CGRP, it was exacerbated by capsazepine, CGRP(8-37), L-NAME, and indomethacin. Administration of aminoguanidine, a selective inhibitor of the inducible form of NOS, and NS-398, a selective inhibitor of cyclooxygenase-2, demonstrated no effects on the liver injury or the hepatic levels of 6-keto-PGF(1alpha). These findings strongly suggest that the activation of the sensory neurons helps ameliorate I/R-induced liver injury both by increasing hepatic-tissue blood flow and by limiting inflammatory response through the enhancement of endothelial production of prostacyclin. In the sensory neuron-mediated enhancement of endothelial production of prostacyclin, CGRP-induced activation of both endothelial NOS and cyclooxygenase-1 may be critically involved. SN - 0022-2143 UR - https://www.unboundmedicine.com/medline/citation/12024109/Ischemia/reperfusion_induced_increase_in_the_hepatic_level_of_prostacyclin_is_mainly_mediated_by_activation_of_capsaicin_sensitive_sensory_neurons_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022214302420112 DB - PRIME DP - Unbound Medicine ER -