Effect of nedocromil sodium on allergen-, PAF-, histamine- and bradykinin-induced airways vasodilatation and pulmonary obstruction in the pig.
1. The influence of nedocromil sodium on the nasal and bronchial effects induced by allergen, platelet-activating factor (PAF), capsaicin, histamine and bradykinin aerosol challenge in ascaris-sensitized and pentobarbitone-anaesthetized pigs was studied. Blood flow changes in the bronchial and nasal circulation were measured with ultrasonic flow probes around the supplying arteries, and vascular resistance was calculated. Changes in pulmonary resistance (Rpulm), dynamic compliance (Cdyn), mean arterial pressure (MAP) and heart rate (HR) were also determined. 2. Allergen and PAF aerosol challenge in the lung produced similar effects consisting of both bronchial and nasal vasodilatation, bronchoconstriction (increase in Rpulm and decrease in Cdyn) and increases in MAP and HR. Local pretreatment with nedocromil sodium (80 mg, aerosol) reduced the peak and duration of both the bronchial vasodilatation and increase in Rpulm, while only the duration of the change in Cdyn was significantly decreased. Nedocromil sodium did not alter the increases in MAP and HR. The nasal vasodilatation evoked by PAF, but not allergen, challenge in the lung was reduced by nedocromil sodium. 3. Allergen challenge in the nose induced vasodilatation of long duration which was reduced by local nedocromil sodium pretreatment (50 micrograms kg-1, intra-arterially). 4. The vasodilator response to histamine aerosol was attenuated in the nasal, but not the bronchial circulation by local nedocromil sodium pretreatment. Histamine-induced bronchoconstriction was not altered by nedocromil sodium. 5. Bradykinin aerosol-induced vasodilatation in the nasal and bronchial circulation was markedly and equally reduced by local nedocromil sodium and systemic capsaicin (50 mg kg-1, s.c. 2 days before) pretreatment. 6. In conclusion, nedocromil sodium blocks some local vascular and bronchial effects, but not increases in MAP and HR, induced by allergen and PAF aerosol in the pig. Bradykinin-induced vasodilatation in the airways, which seems to be largely dependent on capsaicin-sensitive sensory nerves, is markedly inhibited by nedocromil sodium pretreatment, whereas capsaicin-induced vasodilatation is not affected by nedocromil sodium. It may be suggested that nedocromil sodium acts by inhibiting some common process involved in the release of mediators from inflammatory cells (when stimulated by allergen and PAF) and sensory nerves (when stimulated by bradykinin and histamine, but not capsaicin).
Alving
K
K
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Matran
R
R
Lundberg
J M
JM
D000485:Allergens / Q000276:immunology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001920:Bradykinin / Q000037:antagonists & inhibitors; D001980:Bronchi / Q000098:blood supply; D002211:Capsaicin / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D008173:Lung Diseases, Obstructive / Q000503:physiopathology*; D017835:Nedocromil; D009666:Nose / Q000098:blood supply; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D015363:Quinolones / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D000485:Allergens; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006633:Histamine Antagonists; D010972:Platelet Activating Factor; D015363:Quinolones; D017835:Nedocromil; D002211:Capsaicin; D001920:Bradykinin