1. Chronic reduction of salt intake can reduce the natriuretic effect of exogenously administered atrial natriuretic factor. The purpose of this study was to elucidate the intrarenal site(s) of such atrial natriuretic factor resistance. Renal clearance and collecting duct microcatheterization experiments were made before and during infusion of atrial natriuretic factor in three groups of rats: group 1 consisted of rats fed a high salt diet (8% NaCl) for 1 week before the experiment; group II were fed a low salt diet (< 0.008%); group III received the same low salt diet, but were acutely replenished with salt at the time of experiment.
2. Baseline sodium chloride excretion was 6480 ± 810 nmol min−1g−1 kidney weight in group 1 compared to 99 ± 16 in group 1. Fractional re-absorptions in the medullary collecting duct were 37 ± 6% and 95 ± 2% of delivered load, respectively (P < 0.05). The fractions of filtered sodium remaining at the beginning of the medullary duct were 6.6 ± 1.0% of filtered load in group 1 and 2.7 ± 0.7% in group II (P < 0.05), indicating increased tubular reabsorption in group II, not only in the medullary duct, but also in upstream nephron segments.
3. During infusion of atrial natriuretic factor, marked saluresis (13240 ± 750 nmol min−1 g−1 kidney weight), together with decreased fractional reabsorption at both sites (duct, −13 ± 9%; upstream remainder, 7.9 ± 0.7%; P < 0.05 each, compared to corresponding control values) was found in group 1, whereas the excretory (150 ± 28 nmol min−1 g−1 kidney weight), and the tubular transport (duct = 84 ± 3%; upstream remainder =2.2 ± 0.4%) changes were quantitatively insignificant in group II. Glomerular filtration rate was increased in group 1 from 1.07 ± 0.03 to 1.26 ± 0.04 ml min−1g−1 kidney weight (P < 0.05), but not in group II (0.93 ± 0.07 to 0.96 ± 0.09, not significant).
4. In group III, acute salt replenishment was associated with increased excretion (1940 ± 440 nmol mm−1 g−1 kidney weight, P < 0.05 compared to group II) and with reduction of tubular reabsorption in the collecting duct only (69 ± 8%, P < 0.05). Infusion of atrial natriuretic factor in this group further increased natriuresis (7810 ± 780 nmol min−1 g−1 kidney weight) and decreased tubular reabsorption in the duct (−32 ± 22%, P < 0.05 compared to the corresponding control value).
5. We conclude that chronic salt deprivation can effectively prevent, via a rapidly reversible counter-regulatory mechanism, the expected actions of atrial natriuretic factor on sodium reabsorption in the medullary collecting duct. Operation of such a mechanism may explain salt retention despite elevated endogenous levels of atrial natriuretic factor in pathological states such as congestive heart failure and liver cirrhosis.
Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy
