title: Increased substance P content in nerve fibers associated with mesenteric veins from deoxycorticosterone acetate (DOCA)-salt hypertensive rats.
abstract: This study examined sensory nerves associated with mesenteric arteries and veins in sham and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Reactivity of arteries and veins to substances released from sensory nerves was also studied in vitro using computer-assisted video microscopy. Co-localization of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactivity (ir) was used to evaluate perivascular sensory nerves. Radioimmunoassay was used to quantify SP- and CGRP-ir content. Immunohistochemical studies revealed a plexus of SP/CGRP-ir nerves associated with arteries and veins. The intensity of SP-ir, but not CGRP-ir labeling was greater in arteries and veins from DOCA-salt compared to sham rats. RIA measurements revealed that the CGRP-ir content of arteries and veins was higher than the SP-ir content but there was a significant increase in SP-ir, but not CGRP-ir, content in arteries and veins from DOCA-salt rats. SP (0.03-1 microM) contracted veins and the NK-3 receptor agonist, senktide, mimicked this effect. There were no differences in SP or senktide reactivity of veins from sham or DOCA-salt rats. SP, but not senktide, relaxed KCl (40 mM) preconstricted arteries. CGRP (0.3 microM), acetylcholine (10 microM) and capsaicin (1 microM) relaxed KCl-preconstricted arteries and veins. The NK-1 receptor agonist, substance P methyl ester relaxed arteries but not veins. These data indicate that DOCA-salt hypertension is associated with upregulation of SP content in perivascular nerves. NK-3 receptors mediate venoconstriction which is unchanged in DOCA-salt hypertension. Increased release of SP from perivenous nerves might contribute to the increased venomotor tone in DOCA-salt hypertension.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA. galliga1@msu.edu
authors.forename: James J
authors.initials: JJ
authors.lastname: Galligan
authors.forename: Sara B
authors.initials: SB
authors.lastname: Miller
authors.forename: Khurshed
authors.initials: K
authors.lastname: Katki
authors.forename: Scott
authors.initials: S
authors.lastname: Supowit
authors.forename: Donald
authors.initials: D
authors.lastname: DiPette
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Fink
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003900:Desoxycorticosterone; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation*; D008642:Mesenteric Veins / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010919:Placebos; D011189:Potassium Chloride / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D010919:Placebos; D018042:Receptors, Neurokinin-3; C054724:senktide; D013373:Substance P; D003900:Desoxycorticosterone; D011189:Potassium Chloride; D015740:Calcitonin Gene-Related Peptide