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Role of spinal nitric oxide synthase-dependent processes in the initiation of the micturition hyperreflexia associated with cyclophosphamide-induced cystitis.
Neuroscience. 2004; 125(3):663-70.N

Abstract

The aim of this study was to examine the participation of nitrergic neurotransmission in the initiation of micturition hyperreflexia associated to cyclophosphamide (CP)-induced cystitis in rats. Micturition threshold volume was significantly reduced 4 h after CP administration (100 mg/kg, i.p.); this reduction was attenuated by intra-arterially injected N(G)-nitro-l-arginine-methyl ester (l-NAME), a non selective nitric oxide synthase (NOS) inhibitor, but not by intravesical infusion of S-methyl-l-thiocitrulline (l-SMTC), another structurally different NOS inhibitor. Interestingly, l-NAME failed to affect micturition threshold volume in normal rats. The magnitude of isolated detrusor strips contractions elicited by either carbachol or nerve activation was significantly reduced in CP-treated rats but was unaffected by the addition of N(G)-nitro-l-arginine (l-NOARG), a nonselective NOS inhibitor. In contrast, intrathecal l-NAME and l-SMTC but not N(G)-nitro-d-arginine-methyl ester (d-NAME) administration augmented the micturition threshold volume in CP-treated rats in an l-arginine preventable manner. As with the systemic injection, intrathecal l-NAME also did not affect the micturition threshold volume in normal rats. Four hours after CP injection, the number of neuronal NOS immunoreactive or nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) positive neurons in spinal lumbosacral segments (L6-S2) was not altered whereas the number of c-Fos immunoreactive neurons increased significantly in the dorsal gray commissural nucleus (DGC), the parasympathetic sacral nucleus (PSN) and lamina X of these segments. Ca(2+)-dependent, but not Ca(2+)-independent NOS activity increased significantly in spinal L6-S2 segments but not in thoracic segments of CP-treated rats. These data indicate that the micturition hyperreflexia observed in the initial hours of CP-induced cystitis is associated with an increase in Ca(2+)-dependent NOS activity in spinal L6-S2 segments suggesting an increased production of nitric oxide (NO). The increased production of NO in these spinal segments appears to be necessary for the initiation of the micturition hyperreflexia.

Authors+Show Affiliations

Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-São Paulo, Brazil. plagos@fmed.edu.uyNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15099680

Citation

Lagos, P, and G Ballejo. "Role of Spinal Nitric Oxide Synthase-dependent Processes in the Initiation of the Micturition Hyperreflexia Associated With Cyclophosphamide-induced Cystitis." Neuroscience, vol. 125, no. 3, 2004, pp. 663-70.
Lagos P, Ballejo G. Role of spinal nitric oxide synthase-dependent processes in the initiation of the micturition hyperreflexia associated with cyclophosphamide-induced cystitis. Neuroscience. 2004;125(3):663-70.
Lagos, P., & Ballejo, G. (2004). Role of spinal nitric oxide synthase-dependent processes in the initiation of the micturition hyperreflexia associated with cyclophosphamide-induced cystitis. Neuroscience, 125(3), 663-70.
Lagos P, Ballejo G. Role of Spinal Nitric Oxide Synthase-dependent Processes in the Initiation of the Micturition Hyperreflexia Associated With Cyclophosphamide-induced Cystitis. Neuroscience. 2004;125(3):663-70. PubMed PMID: 15099680.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of spinal nitric oxide synthase-dependent processes in the initiation of the micturition hyperreflexia associated with cyclophosphamide-induced cystitis. AU - Lagos,P, AU - Ballejo,G, PY - 2003/10/27/accepted PY - 2004/4/22/pubmed PY - 2004/8/3/medline PY - 2004/4/22/entrez SP - 663 EP - 70 JF - Neuroscience JO - Neuroscience VL - 125 IS - 3 N2 - The aim of this study was to examine the participation of nitrergic neurotransmission in the initiation of micturition hyperreflexia associated to cyclophosphamide (CP)-induced cystitis in rats. Micturition threshold volume was significantly reduced 4 h after CP administration (100 mg/kg, i.p.); this reduction was attenuated by intra-arterially injected N(G)-nitro-l-arginine-methyl ester (l-NAME), a non selective nitric oxide synthase (NOS) inhibitor, but not by intravesical infusion of S-methyl-l-thiocitrulline (l-SMTC), another structurally different NOS inhibitor. Interestingly, l-NAME failed to affect micturition threshold volume in normal rats. The magnitude of isolated detrusor strips contractions elicited by either carbachol or nerve activation was significantly reduced in CP-treated rats but was unaffected by the addition of N(G)-nitro-l-arginine (l-NOARG), a nonselective NOS inhibitor. In contrast, intrathecal l-NAME and l-SMTC but not N(G)-nitro-d-arginine-methyl ester (d-NAME) administration augmented the micturition threshold volume in CP-treated rats in an l-arginine preventable manner. As with the systemic injection, intrathecal l-NAME also did not affect the micturition threshold volume in normal rats. Four hours after CP injection, the number of neuronal NOS immunoreactive or nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) positive neurons in spinal lumbosacral segments (L6-S2) was not altered whereas the number of c-Fos immunoreactive neurons increased significantly in the dorsal gray commissural nucleus (DGC), the parasympathetic sacral nucleus (PSN) and lamina X of these segments. Ca(2+)-dependent, but not Ca(2+)-independent NOS activity increased significantly in spinal L6-S2 segments but not in thoracic segments of CP-treated rats. These data indicate that the micturition hyperreflexia observed in the initial hours of CP-induced cystitis is associated with an increase in Ca(2+)-dependent NOS activity in spinal L6-S2 segments suggesting an increased production of nitric oxide (NO). The increased production of NO in these spinal segments appears to be necessary for the initiation of the micturition hyperreflexia. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/15099680/Role_of_spinal_nitric_oxide_synthase_dependent_processes_in_the_initiation_of_the_micturition_hyperreflexia_associated_with_cyclophosphamide_induced_cystitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306452203008388 DB - PRIME DP - Unbound Medicine ER -