Effects of clenbuterol on resting tension and contractile response in vesicourethral smooth muscle of rabbits.
The effects of clenbuterol, a selective beta 2-agonist, on isolated smooth muscle preparations from the rabbit bladder body, bladder base and proximal urethra have been investigated. The inhibitory effects on resting tension and acetylcholine- and field stimulation-induced contractions in the bladder body were compared with those of flavoxate, atropine, and verapamil. Clenbuterol (10(-10)-10(-7) M) had a strong, concentration-dependent relaxant effect on resting tension of the bladder body, and the relaxant effect was antagonized by propranolol. However, clenbuterol had little effect on the bladder base or proximal urethra. Isoproterenol, a non-selective beta agonist, gave a similar result, but was less potent than clenbuterol. Flavoxate failed to reduce the resting tension, but rather enhanced the spontaneous rhythmic contraction in a concentration-dependent manner. Atropine had little effect. Verapamil produced a concentration-dependent relaxation in the bladder body. Acetylcholine-induced contraction in the bladder body was completely inhibited by pretreatment with atropine (10(-7) M). Clenbuterol, flavoxate, and verapamil concentration-dependently inhibited acetylcholine-induced contraction. Field stimulation-induced contraction in the bladder body was not completely inhibited by atropine. However, the residual contraction was completely inhibited by tetrodotoxin. Clenbuterol, flavoxate, and verapamil concentration-dependently inhibited field stimulation-induced contraction. The inhibitory effects of clenbuterol and verapamil were antagonized by an application of propranolol and an increase in external Ca, respectively. The data suggest that the selective relaxant effect of clenbuterol on the bladder body is due to beta 2-antagonistic action, resulting in the inhibition of the contractile response to acetylcholine or field stimulation. Also, its response was different from that of the other drugs used.
Kishimoto
T
T
Pharmacological Research Department, Teijin Institute for Bio-medical Research, Tokyo, Japan.
Aoki
K
K
Okamiya
Y
Y
Takeshita
T
T
Naruchi
T
T
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002976:Clenbuterol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology*; D005422:Flavoxate / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011817:Rabbits; D014521:Urethra / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D005422:Flavoxate; D001285:Atropine; D014700:Verapamil; D000109:Acetylcholine; D002976:Clenbuterol