Pharmacology of the lower urinary tract: basis for current and future treatments of urinary incontinence.
The role of spinal a -adrenergic mechanisms in the control of urinary bladder function was examined in urethane (1.2 g /kg s.c.) 1 anesthetized and decerebrate unanesthetized female Sprague–Dawley rats (250–320 g). Bladder activity was recorded via a transurethral catheter during continuous infusion (0.21 ml /min) cystometrograms or under isovolumetric conditions. All drugs were administered intrathecally at the L -S segmental level of spinal cord. During cystometrograms, 3 or 30 nmol of phenylephrine (a -adrenergic agonist) 6 1 1 did not alter bladder activity; whereas 300 nmol increased the intercontraction interval by 98% and pressure threshold for inducing micturition by 115%, but did not change bladder contraction amplitude. A large dose of phenylephrine (3000 nmol) completely blocked reflex voiding and induced overflow incontinence at a high baseline pressure (mean: 33 cmH O; range: 28–42 cmH O). Under 2 2 isovolumetric conditions, 3–30 nmol of phenylephrine abolished bladder activity for 22–45 min; whereas smaller doses (0.003–0.3 nmol) were inactive. Doxazosin (50 nmol), an a -adrenergic antagonist, decreased intercontraction intervals but did not change bladder 1 contraction amplitude during cystometrograms. Under isovolumetric conditions this dose of doxazosin increased bladder contraction frequency and decreased bladder contraction amplitude. Smaller doses (5 or 25 nmol) of doxazosin did not alter bladder activity. These studies suggest that two types of spinal a -adrenergic mechanisms are involved in reflex bladder activity: (1) inhibitory control of the 1 frequency of voiding reflexes presumably by regulating afferent processing in the spinal cord and (2) facilitatory modulation of the descending limb of the micturition reflex pathway. 2000 Elsevier Science B.V. All rights reserved. Theme: Endocrine and autonomic regulation Topic: Urogenital regulation