Andrzej Wróbel1, Tomasz Rechberger2. 1. Second Department of Gynecology, Medical University of Lublin, Lublin, Poland. Electronic address: wrobelandrzej@yahoo.com. 2. Second Department of Gynecology, Medical University of Lublin, Lublin, Poland.
Abstract
OBJECTIVES: To test the hypothesis that maxacalcitol, vitamin D3 analog, would ameliorate detrusor overactivity (DO) induced by retinyl acetate instillation; to test the outcome of the combined administration of maxacalcitol and the rho kinase inhibitor - GSK 269962, amlodipine besylate, or oxybutynin chloride in this model. METHODS: The rats were treated with maxacalcitol for 14 days. Then, cystometric studies were performed during which the animals were administered test compounds. RESULTS: Maxacalcitol in a dose of 30 but not 15 µg/kg/day induced reduction in DO index, non-voiding contractions frequency (FNVC), and amplitude (ANVC), while increasing volume threshold to elicit non-voiding contractions (VTNVC). The 14-day-long administration of maxacalcitol at a dose of 15 µg/kg/day to animals, followed by GSK 269962 at a single dose of 10 mg/kg, led to a statistically significant reduction of intercontraction interval and bladder compliance, and an increase in DO index, without any effect on ANVC, FNVC, and VTNVC. The assessment of the combined effect of maxacalcitol (15 µg/kg/day) and amlodipine besylate (0.25 mg/kg) demonstrated an increase in intercontraction interval, bladder compliance and VTNVC, with a decrease in FNVC. No statistically significant changes were found in DO index and ANVC. The combined outcome of administering maxacalcitol (15 µg/kg/day) and oxybutynin chloride (0.25 mg/kg) did not show any statistically significant value of the measured cystometric parameters. CONCLUSION: The outcomes of maxacalcitol administration can be the result of 3 mechanisms, that is, the upregulation of L-type Ca(2+) channels, the inhibition of the rho kinase pathway, and a so far unknown central mechanism.
OBJECTIVES: To test the hypothesis that maxacalcitol, vitamin D3 analog, would ameliorate detrusor overactivity (DO) induced by retinyl acetate instillation; to test the outcome of the combined administration of maxacalcitol and the rho kinase inhibitor - GSK 269962, amlodipine besylate, or oxybutynin chloride in this model. METHODS: The rats were treated with maxacalcitol for 14 days. Then, cystometric studies were performed during which the animals were administered test compounds. RESULTS:Maxacalcitol in a dose of 30 but not 15 µg/kg/day induced reduction in DO index, non-voiding contractions frequency (FNVC), and amplitude (ANVC), while increasing volume threshold to elicit non-voiding contractions (VTNVC). The 14-day-long administration of maxacalcitol at a dose of 15 µg/kg/day to animals, followed by GSK 269962 at a single dose of 10 mg/kg, led to a statistically significant reduction of intercontraction interval and bladder compliance, and an increase in DO index, without any effect on ANVC, FNVC, and VTNVC. The assessment of the combined effect of maxacalcitol (15 µg/kg/day) and amlodipine besylate (0.25 mg/kg) demonstrated an increase in intercontraction interval, bladder compliance and VTNVC, with a decrease in FNVC. No statistically significant changes were found in DO index and ANVC. The combined outcome of administering maxacalcitol (15 µg/kg/day) and oxybutynin chloride (0.25 mg/kg) did not show any statistically significant value of the measured cystometric parameters. CONCLUSION: The outcomes of maxacalcitol administration can be the result of 3 mechanisms, that is, the upregulation of L-type Ca(2+) channels, the inhibition of the rho kinase pathway, and a so far unknown central mechanism.
Authors: Alayne D Markland; Vin Tangpricha; T Mark Beasley; Camille P Vaughan; Holly E Richter; Kathryn L Burgio; Patricia S Goode Journal: J Am Geriatr Soc Date: 2018-12-21 Impact factor: 5.562