Effects of Spinal and Peripheral Injection of alpha1A or alpha1D Adrenoceptor Antagonists on Bladder Activity in Rat Models with or without Bladder Outlet Obstruction

Kim, Jae Heon; Shim, Ji Sung; Kang, Seung Chul; Shim, Kang Soo; Park, Jae Young; Moon, Du Geon; Lee, Jeong Gu; Bae, Jae Hyun

Abstract

PURPOSE
Antagonists of alpha1-adrenergic receptors (alpha1ARs) relax prostate smooth muscle and relieve voiding and storage symptoms. Recently, increased expression of alpha1ARs with change of its subtype expression has been proved in bladder outlet obstruction (BOO). To search for the evidence of changes in alpha1ARs subtype expression and activity in the peripheral and spinal routes, the effects of spinal and peripheral administration of tamsulosin (an alpha1A/D-selective AR), naftopidil (an alpha1A/D-selective AR), and doxazosin (non-selective AR) on bladder activity were investigated in a rat model with or without BOO.
METHODS
A total of 65 female Sprague-Dawley rats were divided into the BOO surgery group (n=47) and the sham surgery group (n=18). After 6 weeks, cystometry was assessed before and after intrathecal and intra-arterial administrations of tamsulosin, naftopidil, and doxazosin.
RESULTS
After intra-arterial administrations of all three drugs, bladder capacity (BC) was increased and maximal intravesical pressure (Pmax) was decreased in both BOO and the sham rat models (P<0.05). After intrathecal administration of all three drugs, BC was increased and Pmax was decreased in only the BOO group. The episodes of involuntary contraction in the BOO rat models were decreased by intra-arterial administration (P=0.031). The increase of BC after intrathercal and intra-arterial administrations of alpha1ARs was significantly greater in the BOO group than in the sham group (P=0.023, P=0.041). In the BOO group, the increase of BC and decrease in Pmax were greater by intra-arterial administration than by intrathecal administration (P=0.035). There were no significant differences of the degrees of changes in the cystometric parameters among the three different alpha1ARs.
CONCLUSIONS
Up-regulations of the alpha1ARs in BOO were observed by the greater increases of BC after alpha1AR antagonist administrations in the BOO group than in the sham group. However, there were no subtype differences of the alpha1ARs in functional parameters of bladder activity. In addition, alpha1ARs also act on the lumbosacral cord which implies that the sensitivity of alpha1ARs is increased in pathologic models such as BOO. Further evaluation including differential expression of alpha1ARs in BOO models are need.