FASTING INHIBITS NATRIURETIC PEPTIDES CLEARANCE RECEPTOR EXPRESSION IN RAT ADIPOSE-TISSUE

Objective and design: The early phase of weight loss induced by fastin g is associated with diuresis, natriuresis and reduction in blood pres sure through unclear mechanisms. Atrial natriuretic peptide (ANP) is a cardiac hormone with potent natriuretic, diuretic and hypotensive eff ects mediated by 'biologically active' receptors (NPr-A). A second typ e of receptor mediates the clearance of ANP (the clearance receptor, N Pr-C). Since NPr-C appears to be abundant in adipose tissue, we analys ed NPr-C and NPr-A gene expression in white and brown adipose tissue ( WAT and BAT) as well as in renal cortex of fasting rats. Plasma ANP, c yclic GMP and aldosterone were also measured. Methods: Twelve male Wis tar rats were deprived of food for about 50 h, and 12 other rats were fed ad libitum. Periepididymal WAT, interscapular BAT and left renal c ortex were used for RNA extraction and northern blot analysis with rat NPr-C and NPr-A complementary DNA probes labelled with P-32-dCTP. Den sitometric analysis of hybridization signals was corrected by beta act in expression before statistical analysis. Blood was drawn for ANP, cy clic GMP (cGMP) and aldosterone radioimmunoassays, which were also mea sured in a group of six rats deprived of food for 25 h. Results: A dra matic decrease in NPr-C steady-state messenger RNA levels was observed both in WAT (about 3.6-fold, P<0.001) and in BAT (about threefold, P< 0.01), but fasting did not affect the expression of NPr-A in adipose t issues. In the renal cortex NPr-C and NPr-A messenger RNA levels were unaffected by fasting. ANP and aldosterone levels were reduced after f asting whereas cyclic GMP was increased at 25 h, but the differences d id not reach statistical significance. Conclusions: Fasting exerts a t issue-specific and gene-specific suppression of NPr-C gene expression in adipose tissue that appears to be accompanied by an increased biolo gical activity of ANP. The natriuresis and diuresis and reduction of b lood pressure induced by fasting might result from a reduced expressio n of NPr-C in adipose fat pads.