title: Sympathetic β-adrenergic mechanism in pudendal inhibition of nociceptive and non-nociceptive reflex bladder activity.
abstract: This study investigated the role of the hypogastric nerve and β-adrenergic mechanisms in the inhibition of nociceptive and non-nociceptive reflex bladder activity induced by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats, non-nociceptive reflex bladder activity was induced by slowly infusing saline into the bladder, whereas nociceptive reflex bladder activity was induced by replacing saline with 0.25% acetic acid (AA) to irritate the bladder. PNS was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. During saline infusion, PNS at 2T and 4T significantly (P < 0.01) increased bladder capacity to 184.7 ± 12.6% and 214.5 ± 10.4% of the control capacity. Propranolol (3 mg/kg iv) had no effect on PNS inhibition, but 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP; 1-3 mg/kg iv) significantly (P < 0.05) reduced the inhibition. During AA irritation, the control bladder capacity was significantly (P < 0.05) reduced to ∼22% of the saline control capacity. PNS at 2T and 4T significantly (P < 0.01) increased bladder capacity to 406.8 ± 47% and 415.8 ± 46% of the AA control capacity. Propranolol significantly (P < 0.05) reduced the bladder capacity to 276.3% ± 53.2% (at 2T PNS) and 266.5 ± 72.4% (at 4T PNS) of the AA control capacity, whereas MTEP (a metabotropic glutamate 5 receptor antagonist) removed the residual PNS inhibition. Bilateral transection of the hypogastric nerves produced an effect similar to that produced by propranolol. This study indicates that hypogastric nerves and a β-adrenergic mechanism in the detrusor play an important role in PNS inhibition of nociceptive but not non-nociceptive reflex bladder activity. In addition to this peripheral mechanism, a central nervous system mechanism involving metabotropic glutamate 5 receptors also has a role in PNS inhibition.
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: Brian T
authors.initials: BT
authors.lastname: Kadow
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Lyon
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Urology, Qilu Hospital, Shandong University, Jinan, China; and.
authors.forename: Zhaocun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lamm
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania;
authors.forename: Jicheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: James R
authors.initials: JR
authors.lastname: Roppolo
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania cftai@pitt.edu.
authors.forename: Changfeng
authors.initials: C
authors.lastname: Tai
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002415:Cats; D003714:Denervation; D004558:Electric Stimulation; D005260:Female; D007001:Hypogastric Plexus / Q000503:physiopathology; D008297:Male; D059225:Nociception / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D060525:Pudendal Nerve / Q000502:physiology* / Q000503:physiopathology*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology*
chemical_list: C541428:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)piperidine; D000319:Adrenergic beta-Antagonists; D010880:Piperidines; D011943:Receptors, Adrenergic, beta; D013844:Thiazoles; D011433:Propranolol
keywords: cat; hypogastric; neuromodulation; propranolol; pudendal