ATRIAL NATRIURETIC PEPTIDE IN RENAL GROWTH

点击翻译按钮获取中文摘要

During normal renal growth, renal blood flow (RBF) and glomerular filtration rate (GFR) rise, while the efficiency of urine sodium excretion (UNaV) and diuresis following acute volume expansion also increase. Physiologic adaptation in RBF, GFR, and UNaV are similar in compensatory renal growth resulting from a decrease in renal mass. Although mechanisms underlying these changes remain unknown, a recently discovered hormone, atrial natriuretic peptide (ANP), may play a major role. This peptide has been shown to increase RBF, GFR, UNaV, and urine flow rate. Furthermore, atrial ANP content has been found to increase progressively during development. The purpose of the proposed studies is to examine the regulation of ANP gene transcription, storage, circulating levels, and the physiologic and biochemical renal response to ANP during renal growth in the rat. To determine factors which may influence the ontogeny of ANP, somatic growth will be accelerated by reducing litter size, while renal growth will be enhanced by uninephrectomy. Changes in ANP mRNA levels and distribution will be assessed by Northern and dot blot analysis, and in situ hybridization techniques, using a specific cDNA probe. Atrial ANP content and distribution will be studied by radioimmunoassay of atrial extracts and by immunocytochemistry. The response to synthetic rat ANP infusion and to acute volume expansion will be determined by assay of plasma ANP, and plasma and urinary cyclic GMP, which are stimulated by circulating ANP. The effect of ANP on cyclic GMP production by glomeruli isolated from growing rats will also be measured. A change in glomerular ANP receptor density of affinity as a result of renal growth will be assessed by isolation of glomeruli and tubules for equilibrium binding studies. The functional renal response to acute volume expansion as well as to ANP infusion will be studied by measurement of RBF, GFR and UNaV. The physiologic role of endogenous ANP release will be assessed in additional animals by atrial appendectomy. Since autoregulation of RBF is altered by renal growth, the effects of ANP infusion on RBF will be determined at normal and reduced renal perfusion pressure. Interaction of ANP with angiotension II will also be investigated while varying renal perfusion pressure. By increasing our understanding of the physiologic regulation of ANP during normal and adaptive renal and somatic growth, these studies should benefit infants and children with a variety of renal disorders, as well as renal transplant donors and recipients.