[Antigen-induced airway leakage in asthmatic guinea-pigs and the effects of BRL 55834].
OBJECTIVE
To understand the role of airway leakage in asthma attack and investigate the effects of BRL 55834 on prophylaxis and treatment of asthma.


METHODS
Ten normal and seventeen sensitized guinea-pigs were divided into 5 groups. After being anesthetized, right carotid artery, right jugular vein and trachea were cannulated to monitor systemic blood pressure, inject drugs, mechanical ventilate and record airway insufflation pressure (AIP). All animals were pretreated with atropine and propranolol (1 mg/kg) 30 min before experiment. DMSO or BRL 55834 was administered intravenously 2 min before intravenous injection of evans blue (EB, 30 mg/kg), Ovalbumin (OA, 3 mg/ml) was inhaled using an ultrasonic nebulier for 30 seconds 1 min after injection of EB.


RESULTS
(1) BRL 55834 (8 micrograms/kg) did not inhibit airway leakage in normal guinea-pig; (2) Airway leakage increased in sensitized guinea-pigs significantly after inhaling OA, 87 +/- 19 ng dye/mg tissue vs 53 +/- 7 ng dye/mg tissue in trachea (Tr); 119 +/- 67 ng dye/mg tissue vs 79 +/- 46 ng dye/mg tissue in main bronchus (MB); 65 +/- 44 ng dye/mg tissue vs 46 +/- 17 ng dye/mg tissue in central pulmonary airway (CiPA) and 50 +/- 31 ng dye/mg tissue vs 32 +/- 4 ng dye/mg tissue in peripheral pulmonary airway (PiPA, P < 0.05). (3) BRL 55834 inhibited airway leakage contrast to DMSO, especially in CiPA and PiPA, with an inhibition of 48% (Tr, P < 0.05), 57% (MB, P < 0.01), 44% (CiPA, P < 0.05), and 46% (PiPA, P < 0.05) after injection of BRL 55834 8 micrograms/kg, and 46% (Tr, P < 0.05), 57% (MB, P < 0.01), 56%(CiPA, P < 0.01) and 55% (PiPA, P < 0.01) after injection of BRL 55834 16 micrograms/kg, respectively. (4) BRL 55834 decreased base AIP in all groups, and inhibited OA-induced AIP increasing in sensitized guinea-pigs, with an inhibition of 49% (BRL 55834 8 micrograms/kg) and 57% (BRL 55834 16 micrograms/kg) in contrast to DMSO. BRL 55834 had a little side-effect on cardiovascular system, but without statistical significance.


CONCLUSIONS
Airway leakage is one of the most important components in asthma attack, BRL 55834, a selective potassium channel activator, not only decreases airway leakage, but also inhibits OA-induced increase in airway resistance. All these are beneficial to prophylaxis and treatment of asthma.
Shi
Z
Z
Department of Respiratory Medicine, Chang Zheng Hospital, Second Military Medical University, Shanghai 200003.
Yan
Z
Z
Luo
W
W
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D001578:Benzopyrans / Q000494:pharmacology*; D001980:Bronchi / Q000503:physiopathology*; D002199:Capillary Permeability; D005260:Female; D006168:Guinea Pigs; D008297:Male; D010047:Ovalbumin; D010881:Piperidones / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists*; D005466:Fluorocarbons
D001578:Benzopyrans; D010047:Ovalbumin; D010881:Piperidones; D015221:Potassium Channels; C083517:BRL 55834; D005466:Fluorocarbons