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Increased Rho-kinase-mediated prostate contractions associated with impairment of β-adrenergic-cAMP-signaling pathway by chronic nitric oxide deficiency.

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(ω)-nitro-l-arginine methyl ester (L-NAME, 20mg/kg/day; 4 weeks), after which contractile responses to phenylephrine (α1-adrenoceptor agonist; 1nM to 100µM), carbachol (muscarinic agonist; 1nM to 1mM) and α,β-methylene ATP (P2X receptor agonist; 1-10µM), as well as to electrical-field stimulation (EFS; 1-32Hz) were evaluated. PSM relaxations to isoproterenol (non-selective β-adrenoceptor agonist, 0.1nM to 10µM) and sodium nitroprusside (NO donor, 1nM to 10mM) 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 α,β-methylene ATP were higher in L-NAME (Emax: 3.85±0.25, 3.52±0.35 and 2.03±0.2mN, respectively) compared with control group (Emax: 3.08±0.17, 2.37±0.18 and 1.57±0.18mN, respectively). The PSM contractions induced by EFS were also significantly greater in L-NAME group. Prior incubation with the Rho-kinase inhibitor Y27632 (1µM) 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 β-adrenergic-cAMP-signaling pathway.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Calmasini FB,Leiria LO,Alves Junior MJ,Báu FR,Alexandre EC,Silva FH,Mónica FZ,Antunes E

doi

10.1016/j.ejphar.2015.03.057

subject

Has Abstract

pub_date

2015-07-05 00:00:00

pages

24-30

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(15)00286-1

journal_volume

758

pub_type

杂志文章

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Increased Rho-kinase-mediated prostate contractions associated with impairment of β-adrenergic-cAMP-signaling pathway by chronic nitric oxide deficiency.