| The lower urinary tract is responsible for urine storage and voiding. During the storage phase of the micturition cycle, the bladder relaxes to accommodate increasing volumes of urine at acceptable pressure, and the bladder neck and urethra contract to provide resistance to prevent involuntary leakage. During the micturition phase, the bladder neck and urethral muscles relax, and the detrusor contracts and expel urine without major resistance. The epidemiology studies have shown that diseases of the lower urinary tract are very frequent among the population, which lead to lower urinary tract symptoms (LUTS) and have a significant negative impact on the quality of life. LUTS have components of both storage abnormality symptoms such as urgency, frequency, nocturia, incontinence, and voiding abnormality symptoms including weak stream, intermittency, terminal dribbling, incomplete emptying and urinary retention. The prevalence of LUTS seemed to be related to age rather than sex. LUTS is present in about 16% of the population aged 40 years and over, while bladder outlet obstruction (BOO) caused by benign prostatic hyperplasia (BPH) is reported in about 30% of men aged 50–80 in population-based studies. Stress urinary incontinence, a condition largely affecting the women, has a prevalence of 5 to 37% in the general female population. As the ageing of world population, LUTS is becoming a highly concerned clinical and social problem.There are many factors involve in the pathogenesis of lower urinary tract disorders, including muscarinic receptor and non-adrenergic non-cholinergic (NANC) receptors. Among these, theα1- adrenoceptors (α1-ARs) is particularly important. The autonomic nervous system plays a key role in the regulation of lower urinary tract function. Its sympathetic innervation occurs via the hypogastric nerve arising from the nucleus intermediolateralis of spinal cord segments Th12–L2. When the autonomic nervous excites, noradrenaline released from these nerves can act on the smooth muscle and arise contraction of the muscle, which increase the pressure in prostate and urethra and thus lead to LUTS. Expression ofα1-ARs may change during aging. It is reported thatα1-ARs densities in aortic smooth muscle increased with age, particularlyα1B-AR, which clued an increased function ofα1B-AR on the contraction of blood vessel. Some studies have found smallerα1-ARs-mediated urethra contractility in old rats. The result suggests that theα1-ARs expression in lower urinary tract may change during ageing. Only few studies have addressed in this subject and there are still lots of disputations.To observe the influence of ageing onα1A-AR andα1D-AR density in lower urinary tract, we tested the mRNA and protein expression levels ofα1A-AR andα1D-AR in the rat bladder, prostate and posterior urethra at different age.Materials and Methods: The bladder, prostate and 0.5-cm-long urethra distal to prostate of rats at deferent age (2.5 months, 8 months and 18 months old) were obtain through surgery. The organs were weighed immediately. The mRNA and protein levels ofα1A andα1D adrenoceptor in these tissues were determined with RT-PCR, western blot and immunohistochemistry respectively. The change ofα1A-AR andα1D-AR densities the rat bladder, prostate and posterior urethra with age was observed.Results:①The animals' body weight increased with age (p<0.01). The weight of bladder and prostate also increased but the difference failed to reach statistical significance. Because of the randomicity in cutting the urethra, the posterior urethra weight was not compared.②RT-PCR showed that in the lower urinary tract of rat, the amount ofα1A-AR mRNA was more abundant thanα1D-AR, and that prostate and posterior urethra expressed much moreα1-ARs than bladder. Theα1A- andα1D-AR mRNA level decreased with age, the differences were statistically significant except theα1D-AR mRNA expression between 2.5-month- and 8-month-old rats.③Western blot revealed thatα1D-AR was the predominantα1-AR subtype in the rat lower urinary tract. Taking 2.5-month-old rat as an example, theα1A-AR andα1D-AR was detected in a ratio of 59:41, 69:31 and 64:36 in bladder, posterior urethra and prostate respectively. The western blot confirmed the decrease ofα1A-AR andα1D-AR abundance with age at the protein level.④By immunohistochemistry, theα1-ARs were detected in the ruthenium, smooth muscle and connective tissue of bladder and urethra, as well as in prostate stroma, and were assessed to be downregulated in the old animals.⑤The smooth muscle of prostate stroma was less in the old rats than young ones. Conclusion:α1A-AR andα1D-AR were both expressed in the lower urinary tract, mainly in the urothelium, smooth muscle and connective tissue of bladder and urethra, and prostate stroma. The mRNA and protein expression ofα1A-AR andα1D-AR significantly decreased with age in the rat bladder, prostate and posterior urethra. We also revealed a reduction of smooth muscle content in prostate in old rats. Based on these findings, we hypothesize that the impairedα1-ARs-mediated urethra contractility in old rats is a result of the down regulation ofα1-ARs. The mechanism of this down regulation is not clear now. Asα1-ARs is mainly expressed in the smooth muscle of the prostatic stroma, which has a less relative percent in old rats than young rats, the age related decrease in the abundance of prostaticα1-ARs appears to, at least partly, result from the relative changes in the density of smooth muscle. The alteration of ratio of smooth muscle to epithelium may also explain the increase ofα1-ARs density in the BPH patients, because the increase of stroma is dominant in the enlarged prostate. The study provides a new clew for further research of the pathogenesis of and new drug development for LUTS in old people. |
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