Effect of Selective Prostaglandin E2 EP2 Receptor Agonist CP-533,536 on Voiding Efficiency in Rats with Midodrine-Induced Functional Urethral Obstruction.

OBJECTIVES: We investigated the effect of the selective prostaglandin E2 EP2 receptor agonist CP-533,536 on voiding efficiency in rats with midodrine-induced functional urethral obstruction. METHODS: The effect of CP-533,536 (0.03-0.3 mg/kg, intravenous [i.v.]) on urethral perfusion pressure (UPP) was investigated in anesthetized rats pre-treated with midodrine (1 mg/kg, i.v.), which forms an active metabolite that acts as an α1 -adrenoceptor agonist. The effect of CP-533,536 (0.03-0.3 mg/kg, i.v.) on cystometric parameters was also investigated in anesthetized rats. In addition, the effect of CP-533,536 (0.03-0.3 mg/kg, i.v.) on residual urine volume (RV) and voiding efficiency (VE) was investigated in conscious rats treated with midodrine (1 mg/kg, i.v.). RESULTS: CP-533,536 dose-dependently decreased UPP elevated by midodrine in anesthetized rats. In contrast, CP-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 RV and reduced VE. CP-533,536 dose-dependently ameliorated increases in RV and decreases in VE induced by midodrine. CONCLUSIONS: These results suggest that a selective EP2 receptor agonist could ameliorate the elevation of RV and improve the reduction of VE in rats with functional urethral obstruction caused by stimulation of α1 -adrenoceptors. The mechanism of action might be not potentiation of bladder contraction but rather preferential relief of urethral constriction.

Central action of intraventricularly-injected midodrine in rats.

The aim of the present paper was to investigate the effect of intracerebroventricular (i.v.c.) injections of midodrine on the central nervous system of the rat. It was shown that midodrine increased locomotor activity, decreased body temperature, increased sedation in reserpinized rats and the cataleptic effect of haloperidol. Midodrine enhanced amphetamine-stimulated locomotor activity and reduced the amphetamine and apomorphine sterotypy. Phenoxybenzamine, yohimbine and clonidine inhibited the midodrine-induced hyperactivity. Midodrine depressed the whole brain noradrenaline (NA) and dopamine (DA) concentrations and reduced NA turnover. The results suggest a stimulating action of midodrine on the catecholaminergic neurons.