AIM:To explore whether the balance between endothelin(ET) and nitric oxide(NO) plays an important role in airway hyperresponsiveness of asthmatic rats. METHODS:The tension of isolated perfused rat tracheal rings was measured after ET-1 stimulation and incubation of JKC 302 and L-NAME. RESULTS:ET-1 constricted isolated rat tracheal ring, produced slowly developing and long-lasting contraction. The ET-1-induced contraction response of asthmatic rat tracheal ring was higher than that of normal control group (P＜0.01). JKC 302, a selective ETA receptor antagonist, partly blocked ET-1-induced contraction in asthmatic rat trachea ring. L-NAME significantly augmented the constriction caused by ET-1. CONCLUSION:The effects of ET on bronchomotor tone may be modified by NO as this is a bronchomotor, and the imbalance between ET and NO may play an important role in asthma pathogenesis.

Objective To investigate the role of interleukin-4 (IL-4) and interleukin-5 (IL-5) in the pathogenesis of steroid-resistant (SR) asthma.Methods Fifteen patients with SR asthma and 15 patients with steroid-sensitive (SS) asthma were selected based on their clinical responses to prednisone therapy. The peripheral blood mononuclear cells (PBMCs) were obtained and incubated with phytohemagglutinin (PHA) in vitro for 48 h in the presence or absence of dexamethasone (10-7 mol/L). Expressions of IL-4 and IL-5 mRNA in PBMCs were determined by reverse transcription-polymerase chain reaction (RT-PCR), and mRNA positive PBMCs for IL-4 and IL-5 were measured with in situ hybridization using digoxin-labeled cDNA probes.Results In the absence of dexamethasone, there was no significant difference in the expressions of IL-4 and IL-5 mRNA between SR and SS asthmatics, and the numbers of mRNA positive cells for IL-4 and IL-5 were also similar between these two groups, however, in the presence of dexamethasone (10-7 mol/L), expressions of IL-4 mRNA (P<0.01) and IL-5 mRNA (P<0.05) were significantly inhibited in SS asthmatics, but not in SR asthmatics (P>0.05). The numbers of IL-4 and IL-5 mRNA positive cells decreased from 5.50±1.60 to 2.27±0.98 (P<0.01) and from 5.03±1.29 to 1.67±0.70 (P<0.01), respectively in SS asthmatics, but in the patients with SR asthma, there was no significant change in the number of cells expressing mRNA for IL-4 or IL-5.Conclusion The gene expression of IL-4 and IL-5 in SR asthma was not inhibited by dexamethasone at the concentration of 10-7 mol/L. It is suggested that the relative unresponsiveness of T cells to glucocorticoids and persistent production of cytokines may be one of the mechanisms of steroid resistance in asthma.