title: Long-term sensory denervation by neonatal capsaicin treatment augments sympathetic neurotransmission in rat mesenteric arteries by increasing levels of norepinephrine and selectively enhancing postjunctional actions.
abstract: The present study assessed the long-term effects of sensory denervation on sympathetic innervation in rat mesenteric arteries. Mesenteric arterial beds were isolated from adult rats treated as neonates with capsaicin and from vehicle-treated and untreated rats and perfused at a constant flow rate of 5 ml/min. Frequency-dependent constrictions to electrical field stimulation of sympathetic nerves were markedly augmented in capsaicin-treated rats; maximal constriction was approximately 105% and 169% greater than in vehicle-treated and control preparations, respectively. Maximal contractile responses to norepinephrine (NE) and serotonin (5-HT) were increased by approximately 57% and 85%, respectively, compared with vehicle-treated preparations without a change in the pD2 values. Vasoconstrictions to ATP, vasopressin and KCl were unchanged. In contrast, acute denervation of sensory-motor nerves by in vitro capsaicin treatment had no significant effect on vasoconstrictor responses to electrical field stimulation or to NE, ATP, vasopressin and KCl, although the pD2 value for 5-HT was slightly increased. High-performance liquid chromatographic analysis with electrochemical detection showed an approximately 100% increase in mesenteric arterial NE content after long-term capsaicin treatment. Tissue neuropeptide Y, as assessed by enzyme-linked immunosorbent analysis, was unchanged. In conclusion, long-term sensory denervation of rats produces trophic changes in mesenteric arteries as evidenced by augmented sympathetic vasoconstriction mediated both prejunctionally (increase in tissue NE) and postjunctionally (enhanced responses to NE and 5-HT).
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, England.
authors.forename: V
authors.initials: V
authors.lastname: Ralevic
authors.forename: P
authors.initials: P
authors.lastname: Karoon
authors.forename: G
authors.initials: G
authors.lastname: Burnstock
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000494:pharmacology*; D003714:Denervation; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation* / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects; D009478:Neuropeptide Y / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology
chemical_list: D009478:Neuropeptide Y; D014667:Vasopressins; D012701:Serotonin; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D000241:Adenosine; D002211:Capsaicin; D009638:Norepinephrine