title: Endothelial and potassium channel dependent modulation of noradrenergic vasoconstriction in the pig radial artery.
abstract: The localisation and function of noradrenergic perivascular innervation of the radial artery were examined in a porcine model. Through immunohistochemical techniques, we explored the possible existence of dopamine beta-hydroxylase and choline-acetyltransferase in the nerve fibres supplying the radial artery. Arterial rings suspended in organ baths were used to isometrically record tension in functional tests designed to determine the vasoconstriction response to electrical field stimulation (EFS) or exogenous noradrenaline. Morphological studies revealed the presence of noradrenergic, but not cholinergic, nerve fibres in the tunica adventitia and adventitia-media boundary of the artery wall. EFS-elicited frequency-dependent contractions (EF(50)=3.37+/-0.19 Hz and E(max)=87.7+/-3.8%; n=47) were abolished by tetrodotoxin. The contractile effect was markedly reduced by guanethidine, phentolamine and prazosin and slightly inhibited by rauwolscine, but unaltered by propranolol, atropine, bosentan or capsaicine. Endothelium removal increased EFS-evoked contractions but the addition of L-NOArg, ODQ or indomethacin had no effect. Pre-incubation with tetraethylammonium and 4-aminopyridine, but not glibenclamide, enhanced these neurogenic responses. SOD and apocynin reduced EFS-elicited responses at low frequencies. Exposure of the arterial rings to the same agents did not affect the noradrenaline concentration-response curves except for the alpha-adrenoceptor antagonists. These results led to the conclusions that neurogenic contractions in the pig radial artery are predominantly mediated by noradrenaline released from periarterial adrenergic nerves. This neurogenic vasoconstriction is modulated by a non-NO, non-prostanoid endothelium-dependent relaxing factor and by Ca(2+)-activated and voltage-dependent K(+) channels.
authors.affiliation: Department of Physiology, Faculty of Pharmacy, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Pagán
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Martínez
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Martínez
authors.forename: Medardo
authors.initials: M
authors.lastname: Hernández
authors.forename: Albino
authors.initials: A
authors.lastname: García-Sacristán
authors.forename: Carlos
authors.initials: C
authors.lastname: Correa
authors.forename: Dolores
authors.initials: D
authors.lastname: Prieto
authors.forename: Sara
authors.initials: S
authors.lastname: Benedito
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000033:anatomy & histology / Q000294:innervation / Q000378:metabolism* / Q000601:surgery; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism; D017534:Radial Artery / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D009638:Norepinephrine