[Effects of nitroglycerin on nitric oxide and endothelin derived from bronchial epithelial cells and alveolar macrophages in asthma].
OBJECTIVE
To investigate the changes of nitric oxide(NO) and endothelin(ET) derived from alveolar macrophages(AM) and bronchial epithelial cells (BEC), and the influences of nitroglycerin (NTG) on ET and NO in asthma.


METHODS
BEC and AM from 15 patients with asthma exacerbation and 7 healthy control subjects were isolated and cultured for 48 hours. NO and ET levels in supernatants and expressions of iNOS-mRNA and ET-mRNA from cultured BEC and AM were examined by copper coated cadmiunm reduction, radioimmunoassay and in situ hybridization.


RESULTS
The NO level and the ET level in supernatants, and expressions of iNOS-mRNA and ET-mRNA from BEC and AM of the untreated group were higher than those of other groups (P < 0.05, respectively); The NO level from BEC and AM in supernatants of NTG pretreated group were elevated significantly and the ET level and the expression of iNOS-mRNA and ET-mRNA were lower than those of asthma untreated group (P < 0.05, respectively); The NO, ET levels and expressions of iNOS-mRNA, ET-mRNA derived from AM were higher than those derived from BEC in patients with asthma (P < 0.05, respectively); expression of iNOS-mRNA from BEC and AM were negatively correlated with the NO level in supernatants of cultured BEC and AM from the group pretreated by NTG in asthma (r = -0.60, r = -0.59; P < 0.01). While the expression of iNOS-mRNA and ET-mRNA by BEC and AM from other groups were positively correlated with the NO level and the ET level in supernatants of BEC and AM in asthma (all r > or = 0.902; P < 0.01, respectively).


CONCLUSIONS
BEC and AM from patients with asthma exacerbation secreted a large quantity of NO and ET because of the increased expressions of iNOS-mRNA and ET-mRNA; AM was the main source of elevated NO and ET in airways of patients with asthma exacerbation. NTG directly enhanced the production of NO and significantly inhibited the expression of ET-mRNA, and therefore decreased the production of ET.
Xiang
X
X
Respiratory Department, Second Affiliated Hospital, Hunan Medical University, Changsha 410011.
Zhou
H
H
Chen
P
P
D000328:Adult; D001249:Asthma / Q000378:metabolism / Q000473:pathology*; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D016232:Endothelins / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D005996:Nitroglycerin / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D016232:Endothelins; D014665:Vasodilator Agents; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D005996:Nitroglycerin