RENAL RESISTANCE TO ANF IN SALT-DEPLETED RATS IS INDEPENDENT OF SYMPATHETIC OR ANG-ALDOSTERONE SYSTEMS

Chronic salt depletion was used as a model to study the mechanism of r enal resistance to the natriuretic effect of atrial natriuretic factor (ANF). Rats were pretreated with furosemide and placed on a low-salt diet (<0.008% NaCl) for 1 wk before a clearance experiment. Compared w ith animals on a normal salt diet (0.4% NaCl), the natriuretic reponse to ANF administration was reduced by one order of magnitude and was q uantitatively trivial. To assess the influence of the sympathoadrenerg ic system, different groups of rats were either subjected to acute uni lateral renal denervation, to chronic adrenal enucleation to reduce ci rculating catecholamines, or to pretreatment with 6-hydroxydopamine (O HDA) to destroy sympathetic postganglionic nerve endings. None of thes e treatments was able to fully or even partially restore ANF natriures is. To determine whether an effect of angiotensin on the kidney preven ted the response, the specific receptor antagonist losartan (DuP-753) was administered during the week prior to the experiment. This treatme nt also did not influence ANF resistance. Similarly, bilateral adrenal ectomy 2 wk before the experiment did not affect the renal ANF resista nce in salt-depleted rats. The depressed excretory response could not be explained on the basis of reduced renal perfusion pressure or glome rular filtration rate. We conclude that undetermined compensatory mech anism(s) ensures renal salt conservation in this model in the face of even supraphysiological levels of ANF.