Effects of Glutamate Receptor Antagonists on Lower Urinary Tract Function in Conscious Unanesthetized Rats

Abstract

Objectives. To study the effects of the intrathecal administered glutamate receptor antagonists on the bladder and urethral activities during isovolumetric bladder contraction in conscious normal and chronic spinal rats.

Methods. Twenty-eight female Wistar rats with and without previous spinal cord transection were used. Before and after intrathecal administration of glutamate receptor antagonist, urodymamic parameters under isovolmetric condition of the bladder were analyzed.

Results. In normal rats, MK-801 (noncompetitive N-methyl-D-aspartate [NMDA] receptor antagonist) and LY 293558 (competitive AMPA receptor antagonist) produced a decrease in bladder contraction pressure and urethral activity with dose dependent manner. In chronic spinal rats, detrusor-sphincter dyssynergia (DSD) was developed before drug administration. MK-801 and LY 293558 partially inhibited bladder contraction pressure, and markedly depressed urethral contraction concomitant with bladder contraction. LY 293558 produced urethral relaxation concomitant with bladder contraction.

Conclusions. In both normal rats and chronic spinal rats, two subtypes of glutamate receptors (NMDA and AMPA receptors) in the spinal cord were involoved in the control of bladder and urethral activities. The AMPA receptor in the spinal cord seems to take an important role in the development of DSD.