[Effects of relative imbalance between endothlin-1 and nitric oxide on pathogenesis of the ascaris-induced asthma in dogs].
OBJECTIVE
To investigate the effects of relative imbalance between endothlin-1 (ET-1) and nitric oxide (NO) on pathogenesis of the ascaris-induced asthma in dogs.


METHODS
Allergy induced asthma in dogs was established by inhaling ascaris antigen via an ultrasonic neblizer. At first, effects of ET-1 on respiratory system resistance (Rrs) and compliance (Crs) were studied in asthmatic dogs. Then, the roles of ET-1 and NO in regulating airway hyperresponsiveness (BHR) of asthma were investigated. Finally, effects of ET-1 on airway smooth muscle proliferating were observed.


RESULTS
After intravenous injection of ET-1, there was a significant maximal increase in Rrs with (14.33 +/- 0.53) mm Hg.L-1.s-1 in normal dogs and (30.75 +/- 3.38) mm Hg.L-1.s-1 (P < 0.05) in asthmatic dogs. Also, there was a significant maximal decrease in Crs with (24.9 +/- 1.2) L/mm Hg in normal dogs and (14.8 +/- 0.9) L/mm Hg (P < 0.05) in asthmatic dogs. The dose-dependent bronchoconstriction in dogs was induced by three different doses of ET-1 (0.25, 0.5, 1.0 microgram/kg). ET-1 dose-response curve was significantly shifted upward by L-NMMA (P < 0.05). This effect was inhibited by L-arg (P < 0.05). Histological studies showed that ET-1 can stimulate airway smooth muscle proliferating and thickening after one week of ET-1 (4.0 micrograms/kg) i.v. administration.


CONCLUSIONS
ET-1 might be involved in BHR that may be associated with immediate asthma response (IAR) in asthmatic dogs. ET-1 may be important for airway remodeling. The relative imbalance between ET-1 and NO may contribute to pathogenesis of asthma.
Hu
H
H
Department of Pulmonary Medicine, Chinese PLA General Hospital, Beijing 100853.
Zhu
J
J
Liu
Y
Y
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001200:Ascaris; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004285:Dogs; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007262:Infusions, Intravenous; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine