title: Regional heterogeneity in the reactivity of equine small pulmonary blood vessels.
abstract: Regional differences in large equine pulmonary artery reactivity exist. It is not known if this heterogeneity extends into small vessels. The hypothesis that there is regional heterogeneity in small pulmonary artery and vein reactivity to sympathomimetics (phenylephrine and isoproterenol) and a parasympathomimetic (methacholine) was tested using wire myography on small vessels from caudodorsal (CD) and cranioventral (CV) lung of 12 horses [9 mares, 3 geldings, 8.67 ± 0.81 (age ± SE) yr, of various breeds that had never raced]. To study relaxation, vessels were precontracted with U46619 (10(-6) M). Methacholine mechanism of action was investigated using L-nitroarginine methylester (L-NAME, 100 μM) and indomethacin (10 μM). Phenylephrine did not contract any vessels. Isoproterenol relaxed CD arteries more than CV arteries (maximum relaxation 28.18% and 48.67%; Log IC50 ± SE -7.975 ± 0.1327 and -8.033 ± 0.1635 for CD and CV, respectively, P < 0.0001), but not veins. Methacholine caused contraction of CD arteries (maximum contraction 245.4%, Log EC50 ± SE -6.475 ± 0.3341), and relaxation of CV arteries (maximum relaxation 40.14%, Log IC50 ± SE -6.791 ± 0.1954) and all veins (maximum relaxation 50.62%, Log IC50 ± SE -6.932 ± 0.1986) in a nonregion-dependent manner. L-NAME (n = 8, P < 0.0001) and indomethacin (n = 7, P < 0.0001) inhibited methacholine-induced relaxation of CV arteries, whereas indomethacin augmented CD artery contraction (n = 8, P < 0.0001). Our data demonstrate significant regional heterogeneity in small blood vessel reactivity when comparing the CD to the CV region of the equine lung.
authors.affiliation: Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan; stackalice@gmail.com.
authors.forename: Alice
authors.initials: A
authors.lastname: Stack
authors.affiliation: Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan;
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: Derksen
authors.affiliation: Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan; and.
authors.forename: Kurt J
authors.initials: KJ
authors.lastname: Williams
authors.affiliation: Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan;
authors.forename: N Edward
authors.initials: NE
authors.lastname: Robinson
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan.
authors.forename: William F
authors.initials: WF
authors.lastname: Jackson
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006736:Horses; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000098:blood supply*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009213:Myography / Q000379:methods; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014680:Veins / Q000187:drug effects / Q000502:physiology*
chemical_list: D014662:Vasoconstrictor Agents; D016210:Methacholine Chloride; D010656:Phenylephrine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin
keywords: equine; pulmonary; reactivity; regional; vascular