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Effect of Selective Prostaglandin E 2 EP2 Receptor Agonist CP ‐533,536 on Voiding Efficiency in Rats with Midodrine‐Induced Functional Urethral Obstruction
Author(s) -
KURIHARA Ryoko,
IMAZUMI Katsunori,
TAKAMATSU Hajime,
ISHIZU Kenichiro,
YOSHINO Taiji,
MASUDA Noriyuki
Publication year - 2016
Publication title -
luts: lower urinary tract symptoms
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.451
H-Index - 15
eISSN - 1757-5672
pISSN - 1757-5664
DOI - 10.1111/luts.12080
Subject(s) - agonist , midodrine , chemistry , receptor , endocrinology , contraction (grammar) , medicine , pharmacology , anesthesia , blood pressure , orthostatic vital signs
Objectives We investigated the effect of the selective prostaglandin E 2 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 α 1 ‐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 α 1 ‐adrenoceptors. The mechanism of action might be not potentiation of bladder contraction but rather preferential relief of urethral constriction.