Akira Furuta1, Yasuyuki Suzuki2, Taro Igarashi3, Yusuke Koike3, Shin Egawa3, Naoki Yoshimura4. 1. Department of Urology, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi Minato-ku, Tokyo, 105-8461, Japan. a-furuta@rf7.so-net.ne.jp. 2. Department of Urology, Tokyo Metropolitan Rehabilitation Hospital, 2-14-1 Tsutsumitouri Sumida-ku, Tokyo, 131-0034, Japan. 3. Department of Urology, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi Minato-ku, Tokyo, 105-8461, Japan. 4. Department of Urology, University of Pittsburgh School of Medicine, Suite 700, Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA, 15213-3221, USA.
Abstract
PURPOSE: To investigate the effects of combined treatment of tadalafil (a phosphodiesterase-5 inhibitor) and tamsulosin (an α1-adrenoceptor antagonist) on bladder dysfunction in a rat model of bladder outlet obstruction (BOO). METHODS: Cystometry was performed in conscious female BOO rats 6 weeks after partially ligation of the urethra. Either tadalafil (0.03, 0.1 and 0.3 mg/kg) or tamsulosin (0.001, 0.003 and 0.01 mg/kg) was cumulatively applied intravenously at 30-min intervals to examine changes in cystometric parameters and blood pressures. Changes in cystometric parameters and blood pressures were also checked when tadalafil (0.3 mg/kg), tamsulosin (0.003 mg/kg) or both were intravenously applied. RESULTS: In BOO rats, application of either tadalafil (0.3 mg/kg) or tamsulosin (0.003, 0.01 mg/kg) alone significantly increased threshold pressures and intercontraction intervals whereas there were no significant changes in other cystometric parameters. In addition, because a significant reduction in blood pressures was detected after the administration of tamsulosin (0.01 mg/kg), tamsulosin at a lower dose (0.003 mg/kg) was used for the combined treatment. The combination therapy of tadalafil and tamsulosin induced a significantly larger rate of increase in intercontraction intervals (1.7 times) compared with monotherapy of either drug (1.3 times each) although the combined therapy did not affect blood pressures. CONCLUSIONS: These results suggest that the combination therapy of tadalafil and tamsulosin can induce the additive inhibitory effects on urinary frequency compared with monotherapy, more likely via inhibition of the afferent limb of micturition reflex rather than the efferent function as evidenced by the increases in threshold pressures and intercontraction intervals without affecting bladder contractile function.
PURPOSE: To investigate the effects of combined treatment of tadalafil (a phosphodiesterase-5 inhibitor) and tamsulosin (an α1-adrenoceptor antagonist) on bladder dysfunction in a rat model of bladder outlet obstruction (BOO). METHODS: Cystometry was performed in conscious female BOO rats 6 weeks after partially ligation of the urethra. Either tadalafil (0.03, 0.1 and 0.3 mg/kg) or tamsulosin (0.001, 0.003 and 0.01 mg/kg) was cumulatively applied intravenously at 30-min intervals to examine changes in cystometric parameters and blood pressures. Changes in cystometric parameters and blood pressures were also checked when tadalafil (0.3 mg/kg), tamsulosin (0.003 mg/kg) or both were intravenously applied. RESULTS: In BOO rats, application of either tadalafil (0.3 mg/kg) or tamsulosin (0.003, 0.01 mg/kg) alone significantly increased threshold pressures and intercontraction intervals whereas there were no significant changes in other cystometric parameters. In addition, because a significant reduction in blood pressures was detected after the administration of tamsulosin (0.01 mg/kg), tamsulosin at a lower dose (0.003 mg/kg) was used for the combined treatment. The combination therapy of tadalafil and tamsulosin induced a significantly larger rate of increase in intercontraction intervals (1.7 times) compared with monotherapy of either drug (1.3 times each) although the combined therapy did not affect blood pressures. CONCLUSIONS: These results suggest that the combination therapy of tadalafil and tamsulosin can induce the additive inhibitory effects on urinary frequency compared with monotherapy, more likely via inhibition of the afferent limb of micturition reflex rather than the efferent function as evidenced by the increases in threshold pressures and intercontraction intervals without affecting bladder contractile function.
Authors: Javier Angulo; Pedro Cuevas; Argentina Fernández; José M La Fuente; Antonio Allona; Ignacio Moncada; Iñigo Sáenz de Tejada Journal: J Sex Med Date: 2012-07-03 Impact factor: 3.802