Atrial natriuretic factor (ANF) and ANF receptor C gene expression and localization in the respiratory system: effects induced by hypoxia and hemodynamic overload.

Atrial natriuretic factor (ANF) and ANF receptor C (ANF.RC) expression have been investigated in healthy and cardiomyopathic hamsters (CMPH) with widespread necrosis of the diaphragm and myocardium leading to respiratory and heart failure. ANF- and ANF.RC-producing cells were localized in different structures of the respiratory system, and the regulation of their expression by the individual and/or combined action of hypoxia and hemodynamic overload was analyzed. The study was performed in 20-, 90-, and 150-day-old animals using immunohistochemistry, in situ hybridization, Northern blot, and RIA analyses. ANF was shown to be expressed in the tracheo-bronchial epithelium and muscle and, to a lesser extent, in the alveolar wall and muscular media of the pulmonary arteries and extraparenchymal pulmonary veins in both healthy hamsters and CMPH. In 150-day-old CMPH, hypoxia (PaO2 < 50 mm Hg) induced a 10-fold increase in ANF messenger RNA accumulation and a 6-fold increase in the immunoreactive ANF (IR-ANF) concentration in lungs, as quantitated by RIA. As plasma IR-ANF concentrations were elevated in all CMPH age groups, it was most likely produced by the myocardium. ANF.RC messenger RNA was homogeneously distributed throughout the entire respiratory system and was increased 2-fold in hypoxic 150-day-old CMPH only. These results suggest that ANF originating in the respiratory system exerts only paracrine effects on different structures of the respiratory system in addition to the action of circulating ANF. Hemodynamic overload (left ventricular end-diastolic pressure, 17.20 +/- 3.80 mm Hg) might contribute to enhanced ANF gene expression only in extraparenchymal pulmonary vein walls of 150-day-old CMPH. We also propose that ANF.RC overexpression might be a protective mechanism operated via either ANF clearance or inhibition of adenylate cyclase activity to counteract exaggerated smooth muscle relaxation.