Isoprostane 8-epi PGF2α, a product of oxidative stress, is synthesized in the bladder and causes detrusor smooth muscle contraction
✍ Scribed by Tufan Tarcan; Mike B. Siroky; Robert J. Krane; Kazem M. Azadzoi
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 133 KB
- Volume
- 19
- Category
- Article
- ISSN
- 0733-2467
No coin nor oath required. For personal study only.
✦ Synopsis
Isoprostane 8-epi PGF2␣ is a product of oxidative stress that causes potent smooth muscle contraction. Its production increases in conditions associated with oxidative stress such as in diabetes, smoking, and aging. The aim was to study whether the urinary bladder synthesizes isoprostane 8-epi PGF2␣ and releases to the urine and whether isoprostane 8-epi PGF2␣ causes bladder smooth muscle contraction. Urine samples were obtained transurethrally from 12 male New Zealand white rabbits for measurement of isoprostane 8-epi PGF2␣ levels. To examine whether bladder synthesizes isoprostane 8-epi PGF2␣, both ureters were ligated, then the bladder was washed 5 times by filling and emptying with normal saline. Bladder was refilled with normal saline, and at 5 minutes a bladder washout sample was taken. After this, the bladder was contracted by nerve stimulation periodically for 30 minutes, and then another washout sample was taken. Strips of bladder tissues were processed for study of isoprostane 8-epi PGF2␣ production in tissue culture chambers and for isometric tension measurements in the organ bath. Enzyme immunoassay (EIA) revealed a remarkable amount of isoprostane 8-epi PGF2␣ in the rabbit urine. EIA of washout samples showed that the bladder synthesizes isoprostane 8-epi PGF2␣ and its production increases with nerve stimulation-induced contractions. EIA of samples from the tissue culture media showed that bladder strips synthesize isoprostane 8-epi PGF2␣ in vitro. Electrical field stimulation (EFS) significantly increased the synthesis and release of isoprostane 8-epi PGF2␣ by the bladder strips. In the organ bath, isoprostane 8-epi PGF2␣ caused concentration-dependent contraction of bladder tissue. While the threshold contraction required smaller concentration of isoprostane 8-epi PGF2␣ (3 nmol) than carbachol (10 nmol), the amplitude of contraction to carbachol was greater than isoprostane 8-epi PGF2␣. Our studies show that the rabbit bladder synthesizes isoprostane 8-epi PGF2␣ and releases it to the urine. Production of isoprostane 8-epi PGF2␣ in the bladder increases with nerve stimulation-induced contraction. Exogenous isoprostane 8-epi PGF2␣ causes significant bladder smooth muscle contraction. Our findings necessitate further studies to evaluate the possible role of oxidative stress and increased isoprostane 8-epi PGF2␣ production in bladder dysfunction.