title: Noradrenergic vasoconstriction of pig prostatic small arteries.
abstract: The current study investigated the distribution of adrenergic nerves and the action induced by noradrenaline (NA) in pig prostatic small arteries. Noradrenergic innervation was visualized using an antibody against dopamine-beta-hydroxylase (DBH), and the NA effect was studied in small arterial rings mounted in microvascular myographs for isometric force recordings. DBH-immunoreactive nerve fibers were located at the adventitia and the adventitia-media border of the vascular wall. Electrical field stimulation (EFS, 1-32 Hz) evoked frequency-dependent contractions that were reduced by guanethidine and prazosin (adrenergic neurotransmission and alpha1-adrenoceptors blockers, respectively) and by the alpha2-adrenoceptor agonist UK 14,304. The alpha2-adrenoceptor antagonist rauwolscine reversed the UK 14,304-produced inhibition. NA produced endothelium-independent contractions that were antagonized with low estimated affinities and Schild slopes different from unity by prazosin and the alpha1A-adrenoceptor antagonist N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha-alpha-dimethyl-1H-indole-3-ethanamine (RS 17053). The alpha1A-adrenoceptor antagonist 5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy) phenyl]-1-piperazinyl]propyl]-2,4-(1H)-pyrimidinedione (RS 100329), which also displays high affinity for alpha1L-adrenoceptors, and the alpha1L-adrenoceptor antagonist tamsulosin, which also has high affinity for alpha1A- and alpha1D-adrenoceptors, induced rightward shifts with high affinity of the contraction-response curve to NA. The alpha1D-adrenoceptor antagonist 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]8-azaspiro[4,5]decane-7,9-dione dihydrochloride (BMY 7378) failed to modify the NA contractions that were inhibited by extracellular Ca2+ removal and by voltage-activated (L-type) Ca2+ channel blockade. These data suggest that pig prostatic resistance arteries have a rich noradrenergic innervation; and NA, whose release is modulated by prejunctional alpha2-adrenoceptors, evokes contraction mainly through activation of muscle alpha1L-adrenoceptors coupled to extracellular Ca2+ entry via voltage (L-type)- and non-voltage-activated Ca2+ channels.
authors.affiliation: Departamento de Fisiología (Fisiología Animal), Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Paz
authors.initials: P
authors.lastname: Recio
authors.forename: Luis M
authors.initials: LM
authors.lastname: Orensanz
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Martínez
authors.forename: Jorge
authors.initials: J
authors.lastname: Navarro-Dorado
authors.forename: Salvador
authors.initials: S
authors.lastname: Bustamante
authors.forename: Albino
authors.initials: A
authors.lastname: García-Sacristán
authors.forename: Dolores
authors.initials: D
authors.lastname: Prieto
authors.forename: Medardo
authors.initials: M
authors.lastname: Hernández
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000294:innervation; D000068438:Brimonidine Tartrate; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006145:Guanethidine / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011467:Prostate / Q000098:blood supply*; D011810:Quinoxalines / Q000494:pharmacology; D013552:Swine; D013941:Thymine / Q000494:pharmacology; D014661:Vasoconstriction; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D007211:Indoles; D010879:Piperazines; D011810:Quinoxalines; C120711:RS 100329; C099495:RS 17053; D015016:Yohimbine; D000068438:Brimonidine Tartrate; C053428:BMY 7378; D013941:Thymine; D009638:Norepinephrine; D011224:Prazosin; D006145:Guanethidine