A NEW NATURIURETIC FACTOR ACTING LIKE LOO P DIURETIC DRUGS - KINETIC-BEHAVIOR IN NORMAL AND HYPERTENSIVE RATS

We have recently described that urines from salt-loaded rats contain a potent natriuretic tactor acting at the Na-K-Cl cotransport system (C IF : ''Cotransport Inhibitory Factor''). Here we investigated the kine tics of the urinary CIF excretion which follows an oral salt-load : (i ) in normal rats, relative to that of the atrial natriuretic peptide ( ANP) and (ii) in an experimental model of salt-dependent genetic hyper tension (Dahl's rats). Thus, Wistar rats were orally loded with 2 % Na Cl for 8 days. Urinary CIF excretion was measured by testing the inhib itory potency of urines on bumetanide-sensitive lithium efflux in lith ium-loaded human erythrocytes. Plasmatic levels of ANP were measured b y radioimmunnoassay. Plasma ANP rapidly and transiently increased duri ng the first 24 hs of salt-load, decreasing thereafter down to normal levels in 6-8 days. Conversely, CIF slowly increased after 24 hs up to maximal constant levels after 5 days of salt-loading. Dahl salt-sensi tive rats exhibited highly significant increases in urinary CIF excret ion with respect to salt-resistant rats. In the basal state (before sa lt-loading) urinary CIF excretion was 101 +/- 13 vs 17.6 +/- 4.5 units /day in salt-sensitive vs. salt-resistant rats (n = 7 for each group, p < 0.001). This difference was maintained after salt loading (3 380 /- 990 vs. 456 +/- 159 units/day, p < 0.05 at day 5). In conclusion, t he results suggest that CIF is a new natriuretic factor which : (i) sh ares some common properties with loop diuretic drugs (furosemide), (ii ) in contrast with the atrial natriuretic peptide, it seems to be a lo ng-term regulator of excess salt intake and (iii) is increased in Dahl salt-sensitive rats, probably as a compensatory mechanism against the tendency to sodium retention which characterizes this model of hypert ension.