Altered contractile sensitivity of isolated bronchial artery to phenylephrine in ovalbumin-sensitized rabbits.
We tested the hypothesis that atopy and/or allergic lung inflammation enhances alpha1-adrenoceptor-mediated contractions of the bronchial artery. Bronchial arterial resistance vessels were isolated from rabbits that had undergone either systemic ovalbumin (OVA) sensitization followed by saline aerosol challenge (OVA/saline rabbits), or OVA sensitization followed by OVA aerosol challenge (OVA/OVA rabbits), or no sensitization followed by saline aerosol challenge (control rabbits). In OVA/OVA rabbits, bronchoalveolar lavage and lung histology revealed lymphocytic and eosinophilic inflammation. Arterial rings were contracted with phenylephrine (PE). In endothelium-intact arteries isolated from OVA/saline and OVA/OVA rabbits, PE responsiveness was enhanced compared with that of arteries isolated from controls. The nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester increased the contractile response to PE in all three experimental groups to a similar degree, suggesting that depressed NOS activity was not involved in the enhanced PE responsiveness in OVA/saline and OVA/OVA rabbits. After endothelium removal, arteries from OVA/saline and control rabbits showed similar PE responsiveness, indicating that the enhancement of PE responsiveness was endothelium dependent, possibly due to an endothelial constricting factor. In OVA/OVA rabbits, endothelium-denuded arteries showed decreased PE responsiveness compared with the other two groups; this difference was abolished by NG-nitro-L-arginine methyl ester. We conclude that systemic sensitization with OVA per se enhances PE-induced contractions of isolated bronchial arteries in rabbits by an endothelium-dependent mechanism and that allergic lung inflammation attenuates this effect by increased nonendothelial NOS activity.
Zschauer
A O
AO
Division of Pulmonary and Critical Care Medicine, Mount Sinai Medical Center, University of Miami School of Medicine, Miami Beach, Florida 33140, USA. azschaue@med.miami.edu
Sielczak
M W
MW
Wanner
A
A
D000818:Animals; D001981:Bronchial Arteries / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D008168:Lung / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010047:Ovalbumin / Q000276:immunology; D010656:Phenylephrine / Q000494:pharmacology*; D011014:Pneumonia / Q000503:physiopathology; D011817:Rabbits; D012130:Respiratory Hypersensitivity / Q000473:pathology / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D010047:Ovalbumin