Pharmacological analysis of the noradrenergic control of central sympathetic and somatic reflexes controlling the lower urinary tract in the anesthetized cat.
Norepinephrine (NE)-containing terminals densely innervate sympathetic preganglionic neurons in the intermediolateral nucleus and somatic motor neurons in Onuf's nucleus that project through the hypogastric and pudendal nerves, respectively, to innervate the lower urinary tract. In the present study, we pharmacologically analyzed the role of noradrenergic systems on the sympathetic and somatic pathways to the lower urinary tract and asked: 1) Are alpha-1, alpha-2, or beta-adrenergic receptors tonically active along sympathetic and/or somatic reflex pathways? And 2) what is the net effect of increasing the extracellular levels of NE by administration of a NE reuptake inhibitor? To address these questions, we recorded evoked potentials from the central ends of the hypogastric and pudendal nerves in response to electrical stimulation of the pelvic and pudendal nerves in chloralose-anesthetized cats, and the effects of prazosin (1-300 micrograms/kg i.v.), an alpha-1-adrenergic receptor antagonist; idazoxan (1-300 micrograms/kg i.v.), an alpha-2-adrenergic receptor antagonist; propranolol (1 mg/kg i.v.), a beta-adrenergic receptor antagonist; and tomoxetine (0.003-3 mg/kg i.v.), a selective NE reuptake inhibitor, were examined. The results indicate that facilitatory alpha-1-adrenergic receptors are tonically active along both sympathetic and somatic reflex pathways, whereas inhibitory alpha-2-adrenergic receptors are not tonically active. The net effect of acute inhibition of NE reuptake along sympathetic reflex pathways is increased activation of inhibitory alpha-2-adrenergic receptors. Along somatic reflex pathways, increased activation of both facilitatory alpha-1- and inhibitory alpha-2-adrenergic receptors were recorded after acute NE reuptake inhibition. No role for central beta-adrenergic receptors was noted.
Danuser
H
H
Department of Urology, Berne University, Switzerland.
Bemis
K
K
Thor
K B
KB
D000758:Anesthesia; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D002415:Cats; D004146:Dioxanes / Q000494:pharmacology; D019329:Idazoxan; D009046:Motor Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D012018:Reflex / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000502:physiology*; D014551:Urinary Tract / Q000294:innervation*
D004146:Dioxanes; D011437:Propylamines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D000069445:Atomoxetine Hydrochloride; D011433:Propranolol; D009638:Norepinephrine; D011224:Prazosin; D019329:Idazoxan