STIMULATION OF BLADDER ACTIVITY BY VOLUME, L-DOPA AND CAPSAICIN IN NORMAL CONSCIOUS RATS - EFFECTS OF SPINAL ALPHA(1)-ADRENOCEPTOR BLOCKADE

To study possible differences in alpha(1)-adrenoceptor involvement in the spinal mechanisms mediating bladder activity induced by volume (bl adder filling), central (L-dopa), and peripheral (capsaicin) stimulati on, we investigated if these types of bladder activity were modified b y intrathecal (i.t.) or intra-arterial (i.a.) administration of the al pha(1)-adrenoceptor antagonist, indoramin. Indoramin is selective for the alpha(1A)-adrenoceptor subtype, whereas most clinically used alpha (1)-adrenoceptor antagonists, including doxazosin, have no subtype sel ectivity. The drug effects were studied by continuous cystometry in no rmal, conscious rats and rats with bladder activity evoked by intraper itoneal L-dopa (50 mg/kg after carbidopa pretreatment), or by intraves ical capsaicin (30 mu M). I.t. indoramin (50 nmol) significantly decre ased micturition pressure, and increased bladder capacity and micturit ion volume. Dribbling incontinence due to urinary retention was observ ed in one of ten rats. L-dopa-stimulated bladder overactivity was sign ificantly attenuated by i.t. or i.a. indoramin (50 nmol). Similar effe cts of i.t. and i.a. doxazosin (50 nmol) have been reported previously . Intravesical capsaicin (30 mu M) caused bladder activity, which was attenuated by i.t. indoramin (50 nmol), but not by i.t. doxazosin (50 nmol). I.a. indoramin did not reduce capsaicin-induced bladder activit y; doxazosin was moderately effective. The results suggest that the bu lbospinal micturition reflex evoked by alpha(1) bladder filling and L- dopa involves a descending pathway where transmission is partly mediat ed by spinal alpha(1)-adrenoceptors. Bladder overactivity evoked by in travesical capsaicin, which elicits a vesico-spinal-vesical reflex, wa s not affected by i.t. doxazosin in a dose that attenuates activity me diated through the bulbo-spinal pathway. This suggests less involvemen t of spinal alpha(1)-adrenoceptors in the vesico-spinal-vesical than i n the bulbo-spinal voiding reflex.