title: Role of noradrenergic pathways in sneeze-induced urethral continence reflex in rats.
abstract: To clarify the role of noradrenergic pathways in preventing stress urinary incontinence (SUI) during sneezing, we investigated the effect of the norepinephrine reuptake inhibitor nisoxetine and alpha-adrenoceptor antagonists phentolamine (nonspecific blocker) and prazosin (alpha(1)-receptor-selective blocker) on the neurally evoked urethral continence reflex induced by sneezing in rats. The amplitude of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the midurethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats and rats with SUI induced by vaginal distention (VD). In normal rats, intrathecal (it) phentolamine (0.02 nmol) and prazosin (0.02 nmol) decreased A-URS by 11.9 and 15.7%, respectively, without affecting UBP. In both normal and VD rats, intravenous (iv) application of nisoxetine (1 mg/kg) increased A-URS by 17.2 and 18.3% and UBP by 23.7 and 32.7%, respectively. Phentolamine or prazosin (both it) eliminated nisoxetine-induced increases in A-URS, but not the increases in UBP, which were, however, suppressed by iv phentolamine (5 mg/kg) or prazosin (1 mg/kg). Sneezing induced fluid leakage from the urethral orifice in VD rats, but not in normal rats. In VD rats, S-LPP was increased by 30.2% by iv nisoxetine. Application of phentolamine and prazosin (both it) decreased S-LPP by 15.7 and 20.6%, respectively, and nisoxetine induced increases in S-LPP to 13.2 and 12.3%, respectively. These results indicate that activation of the noradrenergic system by a norepinephrine reuptake inhibitor can prevent SUI via alpha(1-)adrenoceptors by enhancing the sneeze-induced active urethral closure mechanism at the spinal level and augmenting UBP at the periphery.
authors.affiliation: Dept. of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kaiho
authors.forename: Izumi
authors.initials: I
authors.lastname: Kamo
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Arai
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D005260:Female; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012912:Sneezing / Q000187:drug effects / Q000502:physiology*; D014521:Urethra / Q000187:drug effects / Q000503:physiopathology*; D014550:Urinary Incontinence, Stress / Q000503:physiopathology*; D014621:Vagina / Q000502:physiology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000317:Adrenergic alpha-Antagonists; D005473:Fluoxetine; C011386:nisoxetine; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine