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Effects of β 3 ‐adrenoceptor stimulation on prostaglandin E 2 –induced bladder hyperactivity and on the cardiovascular system in conscious rats
Author(s) -
Takeda Hiroo,
Yamazaki Yoshinobu,
Igawa Yasuhiko,
Kaidoh Kouichi,
Akahane Satoshi,
Miyata Hiroshi,
Nishizawa Osamu,
Akahane Masuo,
Andersson KarlErik
Publication year - 2002
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.10034
Subject(s) - urination , medicine , agonist , heart rate , atropine , blood pressure , endocrinology , carbachol , stimulation , urinary bladder , overactive bladder , mean arterial pressure , anesthesia , urology , urinary system , receptor , alternative medicine , pathology
Aims. To investigate the effects of selective β 2 ‐ and selective β 3 ‐adrenoceptor (AR) agonists on prostaglandin (PG) E 2 ‐induced bladder hyperactivity in conscious free‐moving rats. Methods. Female Sprague‐Dawley rats were anesthetized for implantation of bladder, intravenous, and intra‐arterial catheters. The effects of a β 3 ‐AR agonist (CL316,243) on cystometric and cardiovascular parameters were assessed in conscious rats. Intravesical instillation of PGE 2 (20–60 μM, 6 mL/hr) in conscious rats produced a concentration‐dependent increase in voiding frequency. Results. In this model i.v. CL316,243 (β 3 ‐AR agonist) reduced basal bladder pressure, increased micturition volume, and prolonged micturition interval in a dose‐dependent manner, without affecting threshold pressure or micturition pressure. On the other hand, i.v. procaterol (β 2 ‐AR agonist) did not counteract the bladder hyperactivity. Atropine (muscarinic antagonist) reduced micturition pressure and micturition volume, and shortened micturition interval. CL316,243 slightly decreased mean blood pressure and increased heart rate only when given at high doses (10 and 100 μg/kg, i.v.). In contrast, procaterol caused a significant decrease in mean blood pressure and a significant increase in heart rate. Atropine significantly increased heart rate. Conclusions. The present results clearly demonstrated that the β 3 ‐AR agonist prolonged the micturition interval without producing significant cardiovascular side effects. The human detrusor, like the rat detrusor, relaxes on β 3 ‐AR stimulation. Provided that these results are valid in humans, selective β 3 ‐AR agonists might be clinically useful for controlling a certain type of bladder overactivity. Neurourol. Urodynam. 21:558–565, 2002. © 2002 Wiley‐Liss, Inc.