Airway vasculature after mycoplasma infection: chronic leakiness and selective hypersensitivity to substance P.
Angiogenesis and microvascular remodeling are features of chronic airway inflammation caused by Mycoplasma pulmonis infection in rats. As airway blood vessels undergo remodeling, they become unusually sensitive to substance P-induced plasma leakage. Here we determined whether the remodeled vessels are leaky under baseline conditions, whether their heightened sensitivity is specific to substance P, and whether the leakage is reversible. Four weeks after infection, the amount of baseline leakage of Evans blue in the tracheal mucosa was two to five times the normal level. Gaps < 1 microm in diameter were located between endothelial cells in some remodeled vessels. Substance P, but not platelet-activating factor or 5-hydroxytryptamine, produced an exaggerated leakage response. Inhalation of the beta2-adrenergic receptor agonist salmeterol reduced the leakage by <60%. We conclude that the blood vessel remodeling after M. pulmonis infection is associated with microvascular leakiness due, in part, to the formation of endothelial gaps. This leakage is accompanied by an abnormal sensitivity to substance P but not to platelet-activating factor or 5-hydroxytryptamine and can be reduced by beta2-agonists.
Kwan
M L
ML
Cardiovascular Research Institute and Department of Anatomy, University of California, San Francisco, California 94143, USA.
Gómez
A D
AD
Baluk
P
P
Hashizume
H
H
McDonald
D M
DM
D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000378:metabolism* / Q000473:pathology; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000378:metabolism / Q000473:pathology; D007211:Indoles; D008297:Male; D009175:Mycoplasma Infections / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D009942:Organometallic Compounds; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D000068299:Salmeterol Xinafoate; D012701:Serotonin / Q000494:pharmacology; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms; D013373:Substance P / Q000378:metabolism* / Q000494:pharmacology; D014132:Trachea / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D001993:Bronchodilator Agents; D007211:Indoles; D009942:Organometallic Compounds; D010972:Platelet Activating Factor; D012701:Serotonin; D013373:Substance P; C015445:copper phthalocyanine; D005070:Evans Blue; D000068299:Salmeterol Xinafoate; D000420:Albuterol