Central muscarinic mechanisms regulating voiding in rats

The influence of muscarinic receptor stimulation and blockade on the centra l regulation of micturition was evaluated in conscious female rats. Saline was infused into the bladder to induce repeated bladder contractions and vo iding. Increasing doses of a muscarinic agonist, oxotremorine-M (OXO-M; 0.0 1 to 1 mug/rat) or antagonist, atropine (0.1 to 30 mug/rat) were administer ed. Intrathecal OXO-M (0.1 mug) increased bladder capacity (BC; 85 +/- 17%) , but did not change maximal Voiding pressure (MVP), pressure threshold (PT ), postvoiding intravesical pressure, or voiding efficiency (VE). Intracere broventricular OXO-M (0.1 mug) increased BC (97 +/- 6%), MVP (45 +/- 19%), PT (158 +/- 49%), and reduced VE (-17 +/- 5%). A larger dose of OXO-M (1 mu g, either i.c.v. or i.t.) produced greater changes. These effects were not reproduced by i.v. injections of OXO-M. The effects of OXO-M were blocked b y pretreatment with atropine in a dose (1 mug i.c.v. or i.t.), which alone had no effect on voiding parameters. A larger dose of atropine (10 mug) red uced MP (-31 +/- 7% i.c.v. and -34 +/- 6% i.t.) and VE (-21 +/- 3% i.c.v. a nd -25 +/- 5% i.t.) but increased BC (52 +/- 8% i.c.v.). These results indi cate that activation of muscarinic receptors in the brain or spinal cord ca n suppress voluntary voiding, but also stimulates bladder activity during b ladder filling. The muscarinic inhibitory mechanisms do not appear to be to nically active. The effects of atropine (i.c.v. and i.t.) indicate that mus carinic excitatory mechanisms are tonically active. These findings raise th e possibility that voiding function is regulated by both inhibitory and exc itatory cholinergic mechanisms in the central nervous system.