Nongenomic actions of glucocorticosteroids on the airway vasculature in asthma.
Inhaled glucocorticosteroids (corticosteroids) continue to be the standard treatment for nonexacerbated asthma because of their anti-inflammatory actions. These include effects on the airway vasculature, which participates in the inflammatory process. Corticosteroids are now known to have genomic as well as nongenomic effects that involve different mechanisms of action. The genomic vascular effects of inhaled corticosteroids include a decrease in airway wall hypervascularity (inhibition of angiogenesis), reversal of the increased airway blood flow, and inhibition of vascular hyperpermeability and leukocyte recruitment. In addition, inhaled corticosteroids decrease airway blood flow acutely (within minutes) and reversibly through a nongenomic action that involves noradrenergic neurotransmission. This effect is likely related to the binding of inhaled corticosteroids to the plasma membrane of and the inhibition of the extraneuronal monoamine transporter on airway vascular smooth muscle cells, thereby increasing norepinephrine concentrations at alpha(1)-adrenoceptors and causing airway vascular smooth muscle contraction and a decrease in airway blood flow. Inasmuch as vascular hyperperfusion is a manifestation of airway inflammation, the acute vasoconstriction could also be considered an anti-inflammatory effect of inhaled corticosteroids.
Wanner
Adam
A
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Miami, P.O. Box 016960(R-47), Miami, FL 33101, USA. awanner@miami.edu
Horvath
Gabor
G
Brieva
Jorge L
JL
Kumar
Sunil D
SD
Mendes
Eliana S
ES
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000235:genetics; D000402:Airway Obstruction / Q000503:physiopathology; D000403:Airway Resistance / Q000187:drug effects* / Q000235:genetics; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D001783:Blood Flow Velocity; D001980:Bronchi / Q000098:blood supply* / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects; D016678:Genome; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012680:Sensitivity and Specificity; D014661:Vasoconstriction / Q000187:drug effects
D000305:Adrenal Cortex Hormones