A Possible Role of Lung cAMP and cGMP for Lung Histamine Release during Chronic Hypercapnia

Abstract

The objective of this study is to determine whether chronic hypercapnia, unlike chronic hypoxia, causes lung tissue histamine release and to seek further evidence for our hypothesis that the cyclic nucleotides cAMP and cGMP play a regulatory role for lung histamine storage and release. Rats exposed chronically to hypercapnia (7% CO2) from 1 to 21 days demonstrated an initial decrease of the total lung histamine content: 0.32 ng/μg DNA after 6 days of hypercapnia compared with a control value of 0.75 ng/μg DNA. The decrease in lung histamine content was accompanied by a 3.8-fold increase of the lung tissue cAMP concentration, a 6.3-fold increase of the cGMP concentration, and a 4.1-fold increase of the cGMP/cAMP ratio. The concentration of both nucleotides remained elevated throughout the hypercapnic period, whereas the cGMP/cAMP ratio and the histamine concentration returned to control values. Since the adrenal glands respond to chronic hypercapnia with hypertrophy, we studied the effect of loss of adrenal function on lung tissue cyclic nucleotide and histamine contents. Adrenalectomy depletes lung histamine and leads to a moderate cGMP increase, whereas cAMP is unaffected and the cGMP/ cAMP ratio increases. Adrenalectomy does not potentiate lung histamine depletion in hypercapnic rats but prevents the increase of lung cAMP, and the cGMP accumulation is less than in non-adrenalectomized hypercapnic rats. The results suggest that (1) chronic hypercapnia leads to histamine release from rat lung tissue and (2) the cAMP increase in lung tissue seems to modulate hypercapnic histamine release and to depend on an intact adrenal gland function. The results support our hypothesis that lung histamine release during chronic hypercapnia is mediated by or associated with an increase of the lung tissue cGMP/cAMP ratio.