Zolpidem increases bladder capacity and decreases urine excretion in rats.
OBJECTIVE
To clarify the effects of zolpidem, a gamma-aminobutyric acid (GABA)(A) receptor agonist, on bladder function, and urine production, we investigated the effects of zolpidem administration on bladder overactivity induced by cerebral infarction (CI) and on urine excretion increased by water overloading in Wistar rats.


METHODS
CI was induced by left middle cerebral artery occlusion. The effects on bladder function of zolpidem alone or in combination with the GABA(A) receptor antagonist bicuculline, were then examined in the CI rats using cystometry. The antidiuretic effect of zolpidem was investigated in water-loaded and Brattleboro rats (genetically vasopressin-deficient). Blood samples were collected from water-loaded rats to determine the aldosterone level 1 and 6 hr after zolpidem administration.


RESULTS
Zolpidem increased bladder capacity dose-dependently, but had no significant effect on bladder contraction pressure in CI rats. Bicuculline dose-dependently inhibited zolpidem-induced increases in bladder capacity without affecting bladder contraction pressure. Zolpidem dose-dependently decreased the volume of urine excreted in water-loaded and Brattleboro rats. Compared with the control group, zolpidem significantly increased the aldosterone concentration in the plasma of water-loaded rats 1 hr after administration.


CONCLUSIONS
Zolpidem increased bladder capacity via a GABAergic mechanism in CI rats, and suppressed urine excretion via a pathway that was not through activation of vasopressin V(2) receptors in water-loaded and Brattleboro rats. These results suggest that zolpidem may improve nocturia via an increase in bladder capacity and a decrease in urine excretion.
Yokoyama
Osamu
O
Department of Urology, Faculty of Medical Science, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan.
Matsuta
Yosuke
Y
Yanai-Inamura
Hiroko
H
Watanabe
Mai
M
Ohtake
Akiyoshi
A
Suzuki
Masanori
M
Sasamata
Masao
M
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002544:Cerebral Infarction / Q000150:complications / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007275:Injections, Intravenous; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011910:Rats, Brattleboro; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014554:Urination / Q000187:drug effects*; D014563:Urodynamics; D000077334:Zolpidem
D018755:GABA Agonists; D018756:GABA Antagonists; D011725:Pyridines; D000450:Aldosterone; D000077334:Zolpidem; D001640:Bicuculline