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Atrial natriuretic peptide reduces ischemia/reperfusion-induced spinal cord injury in rats by enhancing sensory neuron activation.
J Pharmacol Exp Ther. 2007 Aug; 322(2):582-90.JP

Abstract

We recently demonstrated that calcitonin gene-related peptide (CGRP) released from sensory neurons reduces spinal cord injury (SCI) by inhibiting neutrophil activation through an increase in the endothelial production of prostacyclin (PGI(2)). Carperitide, a synthetic alpha-human atrial natriuretic peptide (ANP), reduces ischemia/reperfusion (I/R)-induced tissue injury. However, its precise therapeutic mechanism(s) remains to be elucidated. In the present study, we examined whether ANP reduces I/R-induced spinal cord injury by enhancing sensory neuron activation using rats. ANP increased CGRP release and cellular cAMP levels in dorsal root ganglion neurons isolated from rats in vitro. The increase in CGRP release induced by ANP was reversed by pretreatment with capsazepine, an inhibitor of vanilloid receptor-1 activation, or with (9S, 10S, 12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]-benzodiazocine-10-carboxylic acid hexyl ester (KT5720), an inhibitor of protein kinase A (PKA), suggesting that ANP might increase CGRP release from sensory neurons by activating PKA through an increase in the cellular cAMP level. Spinal cord ischemia was induced in rats using a balloon catheter placed in the aorta. ANP reduced mortality and motor disturbances by inhibiting reduction of the number of motor neurons in animals subjected to SCI. ANP significantly enhanced I/R-induced increases in spinal cord tissue levels of CGRP and 6-keto-prostaglandin F(1alpha). a stable metabolite of PGI(2). ANP inhibited I/R-induced increases in spinal cord tissue levels of tumor necrosis factor and myeloperoxidase. Pretreatment with 4'-chloro-3-methoxycinnamanilide (SB366791), a specific vanilloid receptor-1 antagonist, and indomethacin reversed the effects of ANP. These results strongly suggest that ANP might reduce I/R-induced SCI in rats by inhibiting neutrophil activation through enhancement of sensory neuron activation.

Authors+Show Affiliations

Departments of Cardiovascular Surgery, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17522345

Citation

Nakayama, Takuya, et al. "Atrial Natriuretic Peptide Reduces Ischemia/reperfusion-induced Spinal Cord Injury in Rats By Enhancing Sensory Neuron Activation." The Journal of Pharmacology and Experimental Therapeutics, vol. 322, no. 2, 2007, pp. 582-90.
Nakayama T, Harada N, Asano M, et al. Atrial natriuretic peptide reduces ischemia/reperfusion-induced spinal cord injury in rats by enhancing sensory neuron activation. J Pharmacol Exp Ther. 2007;322(2):582-90.
Nakayama, T., Harada, N., Asano, M., Nomura, N., Saito, T., Mishima, A., & Okajima, K. (2007). Atrial natriuretic peptide reduces ischemia/reperfusion-induced spinal cord injury in rats by enhancing sensory neuron activation. The Journal of Pharmacology and Experimental Therapeutics, 322(2), 582-90.
Nakayama T, et al. Atrial Natriuretic Peptide Reduces Ischemia/reperfusion-induced Spinal Cord Injury in Rats By Enhancing Sensory Neuron Activation. J Pharmacol Exp Ther. 2007;322(2):582-90. PubMed PMID: 17522345.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atrial natriuretic peptide reduces ischemia/reperfusion-induced spinal cord injury in rats by enhancing sensory neuron activation. AU - Nakayama,Takuya, AU - Harada,Naoaki, AU - Asano,Miki, AU - Nomura,Norikazu, AU - Saito,Takayuki, AU - Mishima,Akira, AU - Okajima,Kenji, Y1 - 2007/05/23/ PY - 2007/5/25/pubmed PY - 2007/9/21/medline PY - 2007/5/25/entrez SP - 582 EP - 90 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 322 IS - 2 N2 - We recently demonstrated that calcitonin gene-related peptide (CGRP) released from sensory neurons reduces spinal cord injury (SCI) by inhibiting neutrophil activation through an increase in the endothelial production of prostacyclin (PGI(2)). Carperitide, a synthetic alpha-human atrial natriuretic peptide (ANP), reduces ischemia/reperfusion (I/R)-induced tissue injury. However, its precise therapeutic mechanism(s) remains to be elucidated. In the present study, we examined whether ANP reduces I/R-induced spinal cord injury by enhancing sensory neuron activation using rats. ANP increased CGRP release and cellular cAMP levels in dorsal root ganglion neurons isolated from rats in vitro. The increase in CGRP release induced by ANP was reversed by pretreatment with capsazepine, an inhibitor of vanilloid receptor-1 activation, or with (9S, 10S, 12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]-benzodiazocine-10-carboxylic acid hexyl ester (KT5720), an inhibitor of protein kinase A (PKA), suggesting that ANP might increase CGRP release from sensory neurons by activating PKA through an increase in the cellular cAMP level. Spinal cord ischemia was induced in rats using a balloon catheter placed in the aorta. ANP reduced mortality and motor disturbances by inhibiting reduction of the number of motor neurons in animals subjected to SCI. ANP significantly enhanced I/R-induced increases in spinal cord tissue levels of CGRP and 6-keto-prostaglandin F(1alpha). a stable metabolite of PGI(2). ANP inhibited I/R-induced increases in spinal cord tissue levels of tumor necrosis factor and myeloperoxidase. Pretreatment with 4'-chloro-3-methoxycinnamanilide (SB366791), a specific vanilloid receptor-1 antagonist, and indomethacin reversed the effects of ANP. These results strongly suggest that ANP might reduce I/R-induced SCI in rats by inhibiting neutrophil activation through enhancement of sensory neuron activation. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/17522345/Atrial_natriuretic_peptide_reduces_ischemia/reperfusion_induced_spinal_cord_injury_in_rats_by_enhancing_sensory_neuron_activation_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=17522345 DB - PRIME DP - Unbound Medicine ER -