Actas Urológicas Españolas
versión impresa ISSN 0210-4806
GONZALEZ ENGUITA, C. et al. a1-adrenergic receptors categorisation in the detrusor of patients with obstructive BPH: Early study in experimental models. Actas Urol Esp [online]. 2003, vol.27, n.9, pp.684-691. ISSN 0210-4806.
INTRODUCTION: The action of a1-adrenergic receptor antagonists in ameliorating irritation and obstruction in patients with bladder outlet obstruction (due to Benign Prostatic Hyperplasia-BPH) has been demonstrated. Although it is well known that a1-a receptors are responsible for prostate smooth muscle relaxation, the mechanism by which irritative bladder symptoms are improved is unknown. Different a1 receptor subtypes may be involved. The objective of this study is to investigate the changes in the a-adrenergic receptor populations in the obstructed detrusor, and to determine which subtype is proportionally increased in this situation (bladder outlet obstruction). MATERIAL AND METHODS: This was an in vivo study in an experimental model: male NZ (New Zealand) rabbits. The bladder neck of one group of rabbits was obstructed surgically using the technique proposed by Levin et al1,2. Subsequent to bladder catherisation with a 8Fr catheter, the bladder neck was exposed by means of a low medial abdominal incision. The bladder neck was tied with a 2/0 silk thread below the ureteral orifices. The catheter was taken out at the end of the intervention. The rabbits were sacrificed after 4 weeks using intracardiac pentothal and cystectomy was performed. A control group that did not undergo bladder obstruction were also sacrificed at this time, for the comparative study. Part of the detrusor was used for a pathological study and the rest for a physio-pharmacological study in which the organ was placed in a bath of adrenoceptor agonists (phenylephrine and noradrenaline) and antagonists WB101, AH11101A and BMY7378 (antagonists of the a1a, b, d, respectively). RESULTS: The findings of the pathological study show that the bladder wall was thicker in the rabbits that underwent bladder obstruction. The physio-pharmacological studies demonstrate that the detrusor response to the selective a-1 adrenergic agonist was greater in the rabbits that underwent bladder obstruction, however detrusor contractility was decreased (KPSS). With bladder obstruction the a1d receptors were increased. DISCUSSION AND CONCLUSIONS: Receptor-binding studies (Malloy et al)3 aim to differentiate the a-adrenoreceptor populations. These studies identify and quantitate the different receptor subtypes in tissue without taking into account their activity. The isometric and physio-pharmacological tests evaluate active receptors, i.e. those that respond to agonist and antagonist stimuli. This enables detrusor activity to be evaluated accurately. The results obtained in this investigational study support the hypothesis that there is a high statistically significant increase in the a1 adrenergic receptors in the obstructed detrusor. Furthermore, in agreement with previous molecular studies4, during prostate obstruction a1d is the predominate sub-population in the bladder. These findings may have patho-physiological, clinical and pharmacological implications. If this hypothesis which has been demonstrated in an experimental model, is also demonstrated in studies in humans, pharmacological development should not only be focussed on selective a1a receptor antagonists (prostate) but also on those of a1d, for relieving symptoms in patients with bladder outlet obstruction (BPH and prostatism).
Palabras clave : Receptores a-adrenérgicos; HBP (Hiperplasia Benigna de Próstata); Obstrucción vesical; Estudios fisio-farmacológicos "in vitro" e "in vivo"; Fármacos a-agonistas.