title: Nitrergic relaxations and phenylephrine contractions are not compromised in isolated urethra in a rat model of diabetes.
abstract: In vivo experiments in a diabetic rat model revealed compromised nitrergic urethral relaxations and increased sensitivity to adrenergic agonists. This study evaluated contractile and relaxation properties of urethral smooth muscle after streptozotocin (STZ)-induced diabetes, in vitro, with the aim of determining whether in vivo deficiencies are related to smooth muscle dysfunction. Urethral tissue was collected from adult female Sprague-Dawley rats naive, STZ-treated, vehicle-treated and sucrose-fed at 9-12 week post treatment. Strips from proximal, mid, and distal urethra were placed in tissue baths and stimulated using electric field stimulation (EFS) and pharmacological agents. nNOS staining was evaluated using immunohistochemistry. Phenylephrine (PE, 10μM) contracted all urethral strips with the highest amplitude in mid urethra, in all treatment groups. Likewise, EFS-induced relaxation amplitudes were larger and were observed more frequently in mid urethra. Relaxations were inhibited by the NOS inhibitor, L-NAME (1-100μM). Sodium nitroprusside (0.01-1μM), an NO donor, reversed PE-induced contractions. No statistical differences were observed between treatment groups with respect to any parameters. Qualitative immunohistochemistry showed no differences in the urethral nNOS innervation patterns across the treatment groups. In summary, nitrergic relaxations and adrenergic-induced contractions in the isolated diabetic rat urethra display similar properties to controls, suggesting no dysfunction on the nitrergic or alpha1 adrenergic receptor function in the smooth muscle. This further implies that compromised urethral relaxation and increased adrenergic agonist sensitivity observed in vivo in this model may be due to the disruption of neural signaling between the urethra and the spinal cord, or within the CNS.
authors.affiliation: Urogenix, Inc., Durham, NC, United States.
authors.forename: Z
authors.initials: Z
authors.lastname: Al-Noah
authors.affiliation: Urogenix, Inc., Durham, NC, United States.
authors.forename: D
authors.initials: D
authors.lastname: McKenna
authors.affiliation: Urogenix, Inc., Durham, NC, United States.
authors.forename: C
authors.initials: C
authors.lastname: Langdale
authors.affiliation: Urogenix, Inc., Durham, NC, United States.
authors.forename: K B
authors.initials: KB
authors.lastname: Thor
authors.affiliation: Urogenix, Inc., Durham, NC, United States.
authors.forename: L
authors.initials: L
authors.lastname: Marson
authors.affiliation: Urogenix, Inc., Durham, NC, United States.
authors.forename: E
authors.initials: E
authors.lastname: Burgard
authors.affiliation: Urogenix, Inc., Durham, NC, United States. Electronic address: aura240@yahoo.com.
authors.forename: F Aura
authors.initials: FA
authors.lastname: Kullmann
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013566:Sympathomimetics / Q000494:pharmacology; D014521:Urethra
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D013566:Sympathomimetics; D009599:Nitroprusside; D010656:Phenylephrine; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D019331:NG-Nitroarginine Methyl Ester
keywords: NO; NOS; SNP; Streptozotocin; Urethral strips