Physiology and pathophysiology of atrial natriuretic factor in lungs

OBJECTIVE AND DATA SOURCE: Experimental and clinical data reported in the international literature have been collected and critically reviewed to summarize knowledge of the role of atrial natriuretic factor (ANF) in lung physiology and pathophysiology.

Lung contribution to circulating ANF concentration is modest, whereas its capability of degrading ANF is very high, the lung being one of the major sites of ANF catabolism. The impairment of ANF protease activity in lung tissue by hypoxia and pulmonary hypertension could be responsible for the increase in ANF plasma levels observed in several pulmonary pathological conditions. ANF-specific binding sites in lung are reportedly greater than in any other tissue. ANF induces a cGMP-mediated relaxation of central (rather than peripheral) bronchi. ANF bronchodilating effect has also been clinically demonstrated; eg, asthmatic patients show increased plasma ANF levels and exogenous ANF infusion provokes bronchial relaxation comparable with the salbutamol-induced effect. Moreover, ANF determines pulmonary artery vasodilation, thus contributing to improved pulmonary circulation. When pathophysiological levels are present in plasma, ANF influences pulmonary fluid regulation provoking protein mobilization from arteries to the alveolar space whereas ANF pharmacological concentrations re-equilibrate the transwall gradient. A remarkable enhancement of guanylate cyclase activity in lung tissue before hemodynamic modifications by both endogenous end exogenous ANF has been reported in pneumocytes of cardiomyopathic hamsters. On the other hand, ANF infusion provokes a reduction of pulmonary edema induced by pneumotoxic chemicals through a mechanism independent of the natriuretic/hypotensive action of the peptide and not mediated by cGMP.

The modest amount of specific research on ANF effects on lung does not permit a final assessment of natriuretic peptides in pulmonary physiology and pathophysiology. In particular, further investigations are needed to determine the potential clinical relevance of ANF in asthma and pulmonary edema.