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.