title: Elevated guanylate cyclase and cyclic-guanosine monophosphate-dependent protein kinase levels in nasal mucosae of antigen-challenged rats.
abstract: OBJECTIVE
  In patients with severe allergic rhinitis, the most serious symptom is rhinostenosis, which is considered to be induced by a dilatation of plexus cavernosum. The vascular relaxing responses to chemical mediators are mainly mediated by the production of nitric oxide (NO). However, the exact mechanism(s) in nasal venoresponsiveness of allergic rhinitis is not fully understood. In the present study, we investigated the roles of soluble guanylate cyclase (sGC) and cyclic-guanosine monophosphate (c-GMP)-dependent protein kinase G (PKG) in venodilatation of nasal mucosae of antigen-challenged rats.
  
  
  METHODS
  Actively sensitized rats were repeatedly challenged with aerosolized antigen (2,4-dinitrophenylated Ascaris suum). Twenty-four hours after the final antigen challenge, nasal septum mucosa was exposed surgically and observed directly in vivo under a stereoscopic microscope. The sodium nitroprusside (SNP) and 8-Br-cGMP (a PKG activator) were administered into arterial injection, and the venous diameters of nasal mucosa were observed.
  
  
  RESULTS
  The intra-arterial injections of SNP and 8-Br-cGMP-induced venodilatation were significantly augmented in the nasal mucosae of repeatedly antigen-challenged rats. Furthermore, protein expressions of sGC and PKG were significantly increased in nasal mucosae of the antigen-challenged rats.
  
  
  CONCLUSIONS
  The present findings suggest the idea that the promoted cGMP/PKG pathway may be involved in the enhanced NO-induced venodilatation in nasal mucosae of antigen-challenged rats.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Hoshi University, Japan. Electronic address: sakai@hoshi.ac.jp.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hara
authors.forename: Kenji
authors.initials: K
authors.lastname: Todoroki
authors.forename: Yuma
authors.initials: Y
authors.lastname: Igarashi
authors.forename: Miwa
authors.initials: M
authors.lastname: Misawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Chiba
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D017165:Ascaris suum / Q000276:immunology*; D001886:Bordetella pertussis / Q000276:immunology; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004140:Dinitrophenols / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D006241:Haptens / Q000276:immunology; D007269:Injections, Intra-Arterial; D008297:Male; D009297:Nasal Mucosa / Q000098:blood supply* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase; D013997:Time Factors; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage; D014680:Veins / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology
chemical_list: D000947:Antigens, Helminth; D004140:Dinitrophenols; D006241:Haptens; D018160:Receptors, Cytoplasmic and Nuclear; D014665:Vasodilator Agents; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP