The increase in elderly population is becoming a worldwide phenomenon. Projections indicate that Brazil will be the sixth country in number of elderly people in 2020, exceeding 30 million people. Each year 650.000 elderly people are incorporated into the Brazilian population. Recent clinical studies suggest a strong relationship between aging and genitourinary tract diseases, which results in lower urinary tract symptoms (LUTS). LUTS affects both men and women and comprehend several complaints related to urinary bladder storage and voiding problems. Prostatic diseases in men, including benign prostatic hyperplasia (BPH), are highly prevalent and related to LUTS. Experimental studies also show a direct relationship between aging and prostatic changes; however, there are still few studies attempting to understand the prostatic urethra role in this kind of urinary dysfunction. The urethra has an important role in the micturition cycle and acts in synchrony with the detrusor smooth muscle. The main function of urethra is to maintain urinary continence through contraction during the storage phase and relaxation during the voiding phase. However, studies about urethral dysfunction and its physiopathology are still relatively scarce. A preliminary study in our laboratory evaluated the impact of aging in the urethral smooth muscle reactivity in middle-aged rats (10-months old) when compared to young rats (13-weeks). The contractile response to electrical-filed stimulation (neurogenic response), KCl, phenylephrine (alpha 1 agonist) and vasopressin were significantly greater in urethra from middle-aged compared with young group. Aging also significantly reduced urethral relaxations induced by glyceryl trinitrate (NO donor). Micturition alterations were also observed in middle-aged rats, which showed a bladder higher threshold pressure, capacity and compliance. Molecular alterations in the middle-aged rat urethra tissue were also found, like a higher mRNA expression for phosphodiesterase 5 (NO pathway), alpha adrenergic receptors 1A (urethral main contractile mechanism) and gp91phox (NADPH oxidase subunit), associated to a higher local production of reactive oxygen species. The present project aims to study the physiopathology of urethra in animal models of prostatic dysfunction. The objective is to exploit morphofunctional and molecular alterations of the urethral tissue in its main contractile (mediated by alpha 1 adrenoceptors and rho-kinase pathway) and relaxant mechanisms (mediated by beta adrenoceptors activation and NO-cGMP pathway), as well as the oxidative stress modulation. We will compare the rat urethral dysfunction of two animal models: middle-aged and a classical model of BPH induced by testosterone. This study could contribute for the elucidation of the urethral dysfunction and the signaling pathway involved in pathologic conditions of the BPH.
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