Role of alpha1-adrenergic receptors in detrusor overactivity induced by cold stress in conscious rats.
OBJECTIVE
alpha(1)-Adrenergic receptors (ARs) are involved in micturition control both centrally and peripherally. alpha(1)-AR antagonists improve not only voiding but also storage symptoms in patients with bladder outlet obstruction. We investigated the role of alpha(1)-AR mechanisms involved in detrusor overactivity induced by cold stress in conscious rats.


METHODS
Continuous cystometry was performed at room temperature (RT, 28 +/- 2 degrees C) and for 40 min at cold temperature (CT, 4 +/- 2 degrees C). Voiding interval (VI), micturition volume (MV), and bladder capacity (BC) were evaluated before and after intravenous administration of KMD-3213 (selective alpha(1A)-AR antagonist), naftopidil (selective alpha(1D)-AR antagonist), tamsulosin (selective alpha(1A/1D)-AR antagonist), and prazosin (non-selective alpha(1)-AR antagonist). Blood pressure (BP), cumulative voided volume and body temperature were also evaluated.


RESULTS
At RT, none of the AR antagonists caused significant change in the cystometric parameters. During 40 min of cold stress cumulative voided volume and body temperature did not change, but there were significant decreases in VI, MV, and BC. Low doses of the AR antagonists had no effect on CT-induced decreases of these variables. However, high doses of KMD-3213, tamsulosin, naftopidil and prazosin significantly inhibited the CT-induced decreases in VI, MV, and BC. CT caused a significant increase in BP, and this was not affected by low doses of the AR antagonists. However, high doses of prazosin significantly lowered the CT-induced increase of BP.


CONCLUSIONS
Cold stress induces detrusor overactivity and increases BP in conscious rats. These effects are mediated, at least in part, by alpha(1A)-AR and alpha(1D)-AR subtypes and can be prevented/reduced by alpha(1)-AR antagonists.
Chen
Zhong
Z
Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan. chenzhongchina@hotmail.com
Ishizuka
Osamu
O
Imamura
Tetsuya
T
Aizawa
Naoki
N
Igawa
Yasuhiko
Y
Nishizawa
Osamu
O
Andersson
Karl-Erik
KE
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D003080:Cold Temperature; D005260:Female; D007211:Indoles / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D000077409:Tamsulosin; D001743:Urinary Bladder / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000209:etiology / Q000503:physiopathology*
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D009281:Naphthalenes; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D013449:Sulfonamides; C095285:silodosin; D000077409:Tamsulosin; C064357:naftopidil; D011224:Prazosin