Enhanced Activation of Atrial Natriuretic Peptide (ANP) and Natriuretic Peptide Receptor-A (NPRA) in Chronic Cigarette Smoke-Induced Lung Inflammation in Experimental Rats

We sought to determine the circulatory level of atrial natriuretic peptide (ANP) and its receptor (Natriuretic peptide receptor-A) on different (7, 15, 30 and 45) days of cigarette smoke (CS) exposure-induced pulmonary inflammatory condition in experimental rats. The plasma ANP and lung cGMP levels were measured using a commercial ELISA kit. The total cells count (TC), neutrophil (N), and macrophage (M) were quantitated in bronchoalveolar lavage fluid (BALF) isolated from CS and control rat lungs. In addition, mRNA and protein expression profile of natriuretic peptide receptor-A (NPRA) was also quantitated in experimental groups. The TC, N, and M were gradually increased and reached maximum on the 45th day (p < 0.001 respectively) in BALF isolated from CS exposed rat compared with control. Further, Inflammatory markers of histamine and serotonin levels were also progressively increased and reached the maximum at 45 days of CS rats (p < 0.001 respectively) compared with control. The plasma ANP (9.07 ± 0.57 vs 22.01 ± 0.67 pmol/ml) and lung cGMP (8.66 ± 0.80 vs 21.33 ± 0.98 pg/ml) levels were up-regulated starting from 7th day of exposure and reach a maximum on 45 days CS exposed rats (p < 0.001 respectively) as compared with control. Moreover, mRNA and protein expression of NPRA was increased gradually and reached the maximum (threefold and 3.5-fold respectively) on 45th day of CS exposure. Our results demonstrate for the first time that ANP/NPRA an intrinsic anti-inflammatory system of the lung is getting up-regulated during CS exposure.