Effect of Selective Prostaglandin <scp>E₂ EP2</scp> Receptor Agonist <scp>CP</scp>‐533,536 on Voiding Efficiency in Rats with Midodrine‐Induced Functional Urethral Obstruction

<jats:sec><jats:title>Objectives</jats:title><jats:p>We investigated the effect of the selective prostaglandin <jats:styled-content style="fixed-case">E<jats:sub>2</jats:sub> EP2</jats:styled-content> receptor agonist <jats:styled-content style="fixed-case">CP</jats:styled-content>‐533,536 on voiding efficiency in rats with midodrine‐induced functional urethral obstruction.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The effect of <jats:styled-content style="fixed-case">CP</jats:styled-content>‐533,536 (0.03–0.3 mg/kg, intravenous [i.v.]) on urethral perfusion pressure (<jats:styled-content style="fixed-case">UPP</jats:styled-content>) was investigated in anesthetized rats pre‐treated with midodrine (1 mg/kg, i.v.), which forms an active metabolite that acts as an α<jats:sub>1</jats:sub>‐adrenoceptor agonist. The effect of <jats:styled-content style="fixed-case">CP</jats:styled-content>‐533,536 (0.03–0.3 mg/kg, i.v.) on cystometric parameters was also investigated in anesthetized rats. In addition, the effect of <jats:styled-content style="fixed-case">CP</jats:styled-content>‐533,536 (0.03–0.3 mg/kg, i.v.) on residual urine volume (<jats:styled-content style="fixed-case">RV</jats:styled-content>) and voiding efficiency (<jats:styled-content style="fixed-case">VE</jats:styled-content>) was investigated in conscious rats treated with midodrine (1 mg/kg, i.v.).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:styled-content style="fixed-case">CP</jats:styled-content>‐533,536 dose‐dependently decreased <jats:styled-content style="fixed-case">UPP</jats:styled-content> elevated by midodrine in anesthetized rats. In contrast, <jats:styled-content style="fixed-case">CP</jats:styled-content>‐533,536 did not affect maximum voiding pressure, intercontraction interval, or intravesical threshold pressure. In conscious rats, midodrine (1 mg/kg, i.v.) markedly increased <jats:styled-content style="fixed-case">RV</jats:styled-content> and reduced <jats:styled-content style="fixed-case">VE</jats:styled-content>. <jats:styled-content style="fixed-case">CP</jats:styled-content>‐533,536 dose‐dependently ameliorated increases in <jats:styled-content style="fixed-case">RV</jats:styled-content> and decreases in <jats:styled-content style="fixed-case">VE</jats:styled-content> induced by midodrine.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>These results suggest that a selective <jats:styled-content style="fixed-case">EP2</jats:styled-content> receptor agonist could ameliorate the elevation of <jats:styled-content style="fixed-case">RV</jats:styled-content> and improve the reduction of <jats:styled-content style="fixed-case">VE</jats:styled-content> in rats with functional urethral obstruction caused by stimulation of α<jats:sub>1</jats:sub>‐adrenoceptors. The mechanism of action might be not potentiation of bladder contraction but rather preferential relief of urethral constriction.</jats:p></jats:sec>