Autor(es)

Alexandre, Eduardo Costa ; Curiel, Alline Araujo ; Dias, Jessica Mariana ; da Silva, Fabio H. ; Antunes, Edson ; de Oliveira, Mariana G.

• Tipo de documento: Artigo Científico
• Fonte: AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL; v. 262, p. 10-pg., 2025-10-16.

Resumo

Epidemiological studies identify age as the primary unmodifiable risk factor for male lower urinary tract symptoms (LUTS). While research has focused on the bladder and prostate, the urethra remains understudied. This study investigates aging-induced changes in rat urethral structure and function and their impact on voiding. Male Wistar rats, young (3.5 months) and middle-aged (10 months), were used. Cystometry assessed voiding in vivo, and isolated urethras were used in vitro. Middle-aged rats showed irregular micturition with increased basal pressure, bladder capacity, compliance, and non-voiding contractions, suggesting elevated outlet resistance. Histology showed no significant differences. Contractions to electrical-field stimulation and the alpha 1-adrenoceptor agonist phenylephrine were enhanced, along with a twofold increase in alpha 1A-adrenoceptor mRNA. Conversely, relaxation to nitric oxide (NO) donors sodium nitroprusside (SNP) and glyceryl trinitrate (GTN) was reduced, while responses to the cGMP analog 8Br-cGMP and the soluble guanylate cyclase (sGC) stimulator BAY 41-2272 were unchanged. Lower NO levels, despite increased endothelial NO synthase (eNOS) mRNA, were observed in middle-aged urethras, with no changes in neuronal NOS (nNOS) or sGC subunit beta 1. Phosphodiesterase type 5 (PDE5) mRNA was elevated, correlating with reduced basal and SNP-stimulated cGMP. Oxidative stress was evident, with increased superoxide and reduced expression of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT). NADPH oxidase 2 (NOX2) and xanthine dehydrogenase (XDH) mRNA were upregulated, while hypoxia-inducible factor 1-alpha (HIF1 alpha) remained unchanged. In summary, middle-aged rats show urethral hypercontractility, impaired relaxation, and oxidative stress, without tissue remodeling or ischemia. (AU)

• Processo FAPESP: 17/08122-9 - Priapismo e disfunção miccional na Anemia Falciforme: fisiopatologia e novos candidatos a fármacos
• Beneficiário: Fábio Henrique da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 18/09765-3 - Disfunção miccional e prostática em ratos de meia-idade e camundongos obesos: enfoque na NADPH oxidase (NOx)
• Beneficiário: Mariana Gonçalves de Oliveira Taranto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/15175-1 - Modulação da guanilato ciclase solúvel e dos níveis intracelulares de nucleotídeos cíclicos em órgãos do trato urinário inferior e próstata
• Beneficiário: Edson Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/04556-4 - Envelhecimento e hiperplasia prostática: avaliação de alterações funcionais e moleculares em uretra prostática de ratos
• Beneficiário: Eduardo Costa Alexandre
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado