The regulation of water and electrolyte homeostasis is multifactorial and includes the heart and kidneys as important regulatory centers. Within the heart, a recently discovered hormone, atrial natriuretic factor (ANF), has been implicated in the maintenance of water and salt balance. Primarily found in mammalian atria, ANF has been detected in low amounts in several tissues, including lungs. A disorder of the ANF system has been demonstrated in genetically cardiomyopathic hamsters, a model for human congestive cardiomyopathy. Atrial ANF gene expression and storage are decreased during development of this disease, while paradoxically, circulating levels of ANF are increased. We have hypothesized that an extracardiac source may contribute to ANF production in these pathological conditions. In this paper we provide evidence that ANF synthesis is stimulated in the lungs of hamsters during development of cardiomyopathy as revealed by increased ANF mRNA and peptide levels. Furthermore, we show that ANF synthesized in lungs is secreted and has identical chromatographic and biological properties to circulating ANF. The increased production of ANF in lungs may be physiologically important in preventing pulmonary edema. Alternatively, during cardiac dysfunction, lungs may play a compensatory role by increasing their contribution to plasma ANF levels.
J Gutkowska, M Nemer, M J Sole, J Drouin, P Sirois
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