Effects of Vitamin D Analog on Bladder Function and Sensory Signaling in Animal Models of Cystitis

• Published in: Urology (Ridgewood, N.J.) N.J.), 2013-02, Vol.81 (2), p.466.e1-466.e7
• Main Authors: Shapiro, Bennett, Redman, T. Lawton, Zvara, Peter
• Format: Article
• Language: English
• Subjects: Acetic Acid; Animals; Calcitriol - analogs & derivatives; Calcitriol - pharmacology; Cyclophosphamide; Cystitis - chemically induced; Cystitis - complications; Cystitis - physiopathology; Disease Models, Animal; Female; Male; Mice; Mice, Inbred BALB C; Muscle Contraction - drug effects; Pressure; Rats; Rats, Wistar; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - physiology; Sodium Chloride - administration & dosage; Urinary Bladder - drug effects; Urinary Bladder - innervation; Urinary Bladder - physiopathology; Urinary Bladder, Overactive - drug therapy; Urinary Bladder, Overactive - etiology; Urinary Bladder, Overactive - physiopathology; Urology
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2012.10.027

Objective To measure the effects of nonhypercalcemic vitamin D receptor agonist elocalcitol on bladder function in rats with cyclophosphamide-induced cystitis and on bladder function and sensory nerve activity in a mouse with acetic acid-evoked bladder irritation. Materials and Methods Female Wistar rats and male Balb/C mice were gavaged once daily with elocalcitol diluted in miglyol 812 (treatment group) or miglyol alone (control group). On experimental day 12, polyethylene tubing was implanted into the urinary bladder in all the animals. In the mice, a bipolar electrode was positioned under a single postganglionic bladder nerve. At 48 hours after surgery, bladder function was measured in awake, freely moving rats during bladder filling with 0.9% NaCl and both bladder function and sensory nerve activity was measured in awake, restrained mice during continuous intravesical infusion of 0.9% NaCl followed by 0.25% acetic acid. Results In rats, the treatment group showed a significant increase in bladder capacity and decrease in number of nonvoiding bladder contractions. In mice, the filling pressure during saline infusion was similar in both groups; however, during acetic acid infusion, the average filling pressure was significantly increased (47%) in the control group but not in the elocalcitol treatment group. The firing rate at filling pressure for the treatment group was 3.6-fold and 2.7-fold lower than that in the control group during the saline and acetic acid infusion, respectively. Conclusion Oral treatment with elocalcitol suppressed signs of detrusor overactivity in both animal models and exerted strong suppressive effect on urinary bladder sensory signaling during filling in mice.