Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/244072
Type: Artigo
Title: Increased Rho-kinase-mediated prostate contractions associated with impairment of Beta-adrenergic-camp-signaling pathway by chronic nitric oxide deficiency
Author: Calmasini, Fabiano Beraldi
Silveira, Leiria Luiz Osorio| Alves Junior,Marcos Jose
Bau, Fernando Ricardo
Alexandre, Eduardo Costa
Silva,Fabio Henrique
Monica, Fabiola Zakia
Antunes, Edson
Abstract: Impairment of nitric oxide (NO) - cyclic GMP signaling pathway is likely to contribute to human begnin prostate hyperplasia (BPH). In the present study we have used a model of chronic NO synthesis inhibition to evaluate the functional alterations of prostate smooth muscle (PSM) machinery, and involvement of Rho-kinase pathway. Wistar rats were treated with the NO inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg/day; 4 weeks), after which contractile responses to phenylephrine (alpha(1)-adrenoceptor agonist; 1 nM to 100 mu M), carbachol (muscarinic agonist; 1 nM to 1 mM) and alpha,beta-methylene ATP (P2X receptor agonist; 1-10 mu M), as well as to electrical-field stimulation (EFS; 1-32 Hz) were evaluated. PSM relaxations to isoproterenol (non-selective beta-adrenoceptor agonist, 0.1 nM to 10 mu M) and sodium nitroprusside (NO donor, 1 nM to 10 mM) were also evaluated. The ratio prostate weight/body weight was 22% greater (P< 0.05) in L-NAME compared with control group. The PSM contractions to phenylephrine, carbachol and alpha,beta-methylene ATP were higher in L-NAME (E-max: 3.85 +/- 0.25, 3.52 +/- 0.35 and 2.03 +/- 0.2 mN, respectively) compared with control group (E-max: 3.08 +/- 0.17, 2.37 +/- 0.18 and 1.57 +/- 0.18 mN, respectively). The PSM contractions induced by EFS were also significantly greater in L-NAME group. Prior incubation with the Rho-kinase inhibitor Y27632 (1 mu M) fully reversed the enhanced contractions to phenylephrine and carbachol. Isoproterenol-induced PSM relaxations were 34% lower in L-NAME group, which was associated with reduced levels of cAMP in prostate tissue. The relaxations to sodium nitroprusside remained unaltered in L-NAME group. In summary, chronic NO deficiency leads to increased Rho-kinase-mediated PSM contractile responses accompanied by impairment of beta-adrenergic-cAMP-signaling pathway. (C) 2015 Elsevier B.V. All rights reserved.
Impairment of nitric oxide (NO) - cyclic GMP signaling pathway is likely to contribute to human begnin prostate hyperplasia (BPH). In the present study we have used a model of chronic NO synthesis inhibition to evaluate the functional alterations of prostate smooth muscle (PSM) machinery, and involvement of Rho-kinase pathway. Wistar rats were treated with the NO inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg/day; 4 weeks), after which contractile responses to phenylephrine (alpha(1)-adrenoceptor agonist; 1 nM to 100 mu M), carbachol (muscarinic agonist; 1 nM to 1 mM) and alpha,beta-methylene ATP (P2X receptor agonist; 1-10 mu M), as well as to electrical-field stimulation (EFS; 1-32 Hz) were evaluated. PSM relaxations to isoproterenol (non-selective beta-adrenoceptor agonist, 0.1 nM to 10 mu M) and sodium nitroprusside (NO donor, 1 nM to 10 mM) were also evaluated. The ratio prostate weight/body weight was 22% greater (P< 0.05) in L-NAME compared with control group. The PSM contractions to phenylephrine, carbachol and alpha,beta-methylene ATP were higher in L-NAME (E-max: 3.85 +/- 0.25, 3.52 +/- 0.35 and 2.03 +/- 0.2 mN, respectively) compared with control group (E-max: 3.08 +/- 0.17, 2.37 +/- 0.18 and 1.57 +/- 0.18 mN, respectively). The PSM contractions induced by EFS were also significantly greater in L-NAME group. Prior incubation with the Rho-kinase inhibitor Y27632 (1 mu M) fully reversed the enhanced contractions to phenylephrine and carbachol. Isoproterenol-induced PSM relaxations were 34% lower in L-NAME group, which was associated with reduced levels of cAMP in prostate tissue. The relaxations to sodium nitroprusside remained unaltered in L-NAME group. In summary, chronic NO deficiency leads to increased Rho-kinase-mediated PSM contractile responses accompanied by impairment of beta-adrenergic-cAMP-signaling pathway
Subject: Próstata
Óxido nítrico
Quinases associadas a Rho
NG-nitroarginina metil éster
Country: Holanda
Editor: Elsevier
Citation: Increased Rho-kinase-mediated Prostate Contractions Associated With Impairment Of Beta-adrenergic-camp-signaling Pathway By Chronic Nitric Oxide Deficiency. Elsevier Science Bv, v. 758, p. 24-30 Jul-2015.
Rights: fechado
Identifier DOI: 10.1016/j.ejphar.2015.03.057
Address: http://www.sciencedirect.com/science/article/pii/S0014299915002861
Date Issue: 2015
Appears in Collections:FCM - Artigos e Outros Documentos

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