Effects of a combination of herbal extracts (modified Ojayeonjonghwan (Wuzi Yanzong wan)) on partial urethral obstruction-induced detrusor overactivity in rats: impact on the nitric oxide pathway and oxidative stress.

BACKGROUND: We investigated the effects of a berry mixture formula (modified Ojayeonjonghwan (Wuzi Yanzong Wan, MO formula) on detrusor overactivity (DO). METHODS: The MO formula consisted of 5 seeds obtained from 5 types of berry plants. Twenty-four Sprague-Dawley rats were randomly assigned to four groups: sham-operated (control), partial urethral obstruction-induced DO (DO group), 0.03 mg/kg solifenacin-treated DO (solifenacin group) and 200 mg/kg MO formula -treated DO (berry mixture). The control and overactive groups were administered distilled water for 4 weeks, and the solifenacin and MO formula groups were treated with the respective medication for 4 weeks. After treatment, cystometrography was performed. At the endo of cystometrography, their bladder tissues were used for identifying the muscarinic receptors, endothelial nitric oxide synthase(eNOS), RhoA, Rock-I & II, 8-hydroxy-2' -deoxyguanosine(8-OHdG), superoxide dismutase(SOD), interleukin-6 &-8(IL-6, IL-8), and tumor necrosis factor-alpha(TNF-a). The tissues were stained and the muscle-to-collagen ratio was identified. RESULTS: The presence of the muscarinic receptors were not significantly different between the solifenacin and MO formula groups. However, significant differences were found between the solifenacin and MO formula groups in terms of eNOS, RhoA, Rock-I and -II levels. The muscle-to-collagen ratio was statistically lower in the DO and solifenacin groups; however, no significant difference was observed between the control and MO formula groups. Under oxidative stress, SOD showed a similar result as 8-OHgG. The MO formula group exhibited anti-inflammatory effects, showing that no significant difference was found between the control and MO formula groups regarding values of IL-6, IL-8, and TNF-a. However, the DO and solifenacin groups showed increased IL-6, IL-8, and TNF-a levels. Cystometrography showed that the OAB and solifenacin groups having a significantly lower value than the control and MO formula groups. The mean contraction interval was shorter in the DO, MO formula, and solifenacin groups and the highest in the control group. CONCLUSIONS: The MO formula exhibited a similar pharmacologic effect to that of solifenacin, with anti-inflammatory and antioxidant effects. Enhancement of the MO formula by the nitric oxide pathway affected DO including BPH-related DO. The MO formula may be one of the alternative choices of anticholinergics, a treatment for DO.

Reduction of obstruction related bladder overactivity by the guanylyl cyclase modulators BAY 41-2272 and BAY 60-2770 alone or in combination with a phosphodiesterase type 5 inhibitor.

AIMS: To assess the urodynamic effects of soluble guanylyl cyclase (sGC) stimulator, BAY 41-2272, and activator, BAY 60-2770, (which both are able to induce cGMP synthesis even in the absence of nitric oxide (NO)) alone or in combination with a phosphodiesterase type 5 (PDE5) inhibitor, vardenafil, in a model of partial urethral obstruction (PUO) induced bladder overactivity (BO). METHODS: Fifty-six male Sprague-Dawley rats were used, 31 of them underwent PUO. Fourteen rats were used for Western blots to assess PDE5 and sGC expression. For drug evaluation cystometry without anesthesia was performed three days following bladder catheterization. RESULTS: Obstructed rats showed higher micturition frequency and bladder pressures than non-obstructed animals (Intermicturition Interval, IMI, 2.28 ± 0.55 vs. 3.60 ± 0.60 min (± standard deviation, SD); maximum micturition pressure, MMP, 70.1 ± 8.0 vs. 48.8 ± 7.2 cmH2O; both P < 0.05). In obstructed rats vardenafil, BAY 41-2272, and BAY 60-2770 increased IMI (2.77 ± 1.12, 2.62 ± 0.52, and 3.22 ± 1.04 min; all P < 0.05) and decreased MMP (54.4 ± 2.8, 61.5 ± 11.3, and 51.2 ± 6.3 cmH2O; all P < 0.05). When vardenafil was given following BAY 41-2272 or BAY 60-2770 no further urodynamic effects were observed. PDE5 as well as sGC protein expression was reduced in obstructed bladder tissue. CONCLUSIONS: Targeting sGC via stimulators or activators, which increase the levels of cGMP independent of endogenous NO, is as effective as vardenafil to reduce urodynamic signs of BO. Targeting the NO/cGMP pathway via compounds acting on sGC might become a new approach to treat BO.

Characterization of magnesium-induced urinary disease in the cat and comparison with feline urologic syndrome.

Aggregates of struvite crystals caused urethral obstruction in a high percentage of cats fed moist and dry diets supplemented with Mg oxide. Some of the diets were associated with cystolith formation as well. The percentage of Mg in the experimental diets was a misleading indicator of Mg intake because of differences between moist and dry diets in their caloric density. Magnesium homeostasis was maintained in cats ingesting large quantities of Mg. Tissue (kidney, muscle, and rib) concentrations of Mg were the same in cats fed high Mg and control diets. Plasma Mg concentration was increased only in cats ingesting the largest amount of Mg. Magnesium homeostasis was maintained by a marked increase in urine Mg excretion. However, urine Mg concentration was not directly related to Mg intake, apparently because of differences between diets in intestinal absorption of Mg. Urethral obstruction of experimental cats was not associated with a transient increase in Mg intake, nor did obstructing cats have higher urine Mg concentrations than did nonobstructing cats fed the same diet. This observation indicates that factor(s) other than urine Mg concentration are important in urethral obstruction. Cats with urethral obstruction due to naturally occurring disease, feline urological syndrome (FUS), had markedly lower urine Mg concentrations than cats fed high Mg diets. This finding refutes the theory that cats develop FUS because of primary Mg hyperabsorptive phenomena or because of a primary urinary leak of Mg. It also indicates that factors other than urine Mg concentration are involved in the genesis of naturally occurring urethral obstruction. Another difference between the natural and the induced disease was related to the character of the urinary precipitates. Experimental diets higher in Mg concentration caused urolith formation, which is uncommon with FUS. Lower Mg diets caused obstruction with aggregates of crystals, but mucus was not observed. However, in the experimental disease induced in the present study, urinary precipitates were predominantly or exclusively struvite, as has been reported in the natural disease. Many similarities were seen between the diet-induced disease and FUS, but factors in addition to Mg intake are involved in the natural disease. The importance of Mg, compared with the undefined factors, remains to be established.