title: Isoprostane 8-epi PGF2alpha, a product of oxidative stress, is synthesized in the bladder and causes detrusor smooth muscle contraction.
abstract: Isoprostane 8-epi PGF2alpha 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 PGF2alpha and releases to the urine and whether isoprostane 8-epi PGF2alpha causes bladder smooth muscle contraction. Urine samples were obtained transurethrally from 12 male New Zealand white rabbits for measurement of isoprostane 8-epi PGF2alpha levels. To examine whether bladder synthesizes isoprostane 8-epi PGF2alpha, 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 PGF2alpha 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 PGF2alpha in the rabbit urine. EIA of washout samples showed that the bladder synthesizes isoprostane 8-epi PGF2alpha 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 PGF2alpha in vitro. Electrical field stimulation (EFS) significantly increased the synthesis and release of isoprostane 8-epi PGF2alpha by the bladder strips. In the organ bath, isoprostane 8-epi PGF2alpha caused concentration-dependent contraction of bladder tissue. While the threshold contraction required smaller concentration of isoprostane 8-epi PGF2alpha (3 nmol) than carbachol (10 nmol), the amplitude of contraction to carbachol was greater than isoprostane 8-epi PGF2alpha. Our studies show that the rabbit bladder synthesizes isoprostane 8-epi PGF2alpha and releases it to the urine. Production of isoprostane 8-epi PGF2alpha in the bladder increases with nerve stimulation-induced contraction. Exogenous isoprostane 8-epi PGF2alpha causes significant bladder smooth muscle contraction. Our findings necessitate further studies to evaluate the possible role of oxidative stress and increased isoprostane 8-epi PGF2alpha production in bladder dysfunction. Neurourol. Urodynam. 19:43-51, 2000.
authors.affiliation: Department of Urology, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: T
authors.initials: T
authors.lastname: Tarcan
authors.forename: M B
authors.initials: MB
authors.lastname: Siroky
authors.forename: R J
authors.initials: RJ
authors.lastname: Krane
authors.forename: K M
authors.initials: KM
authors.lastname: Azadzoi
mesh_terms: D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D011817:Rabbits; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost