EXTRARENAL RESISTANCE TO ATRIAL-NATRIURETIC-PEPTIDE IN RATS WITH EXPERIMENTAL NEPHROTIC SYNDROME

Nephrotic syndrome is associated with resistance to the renal actions of atrial natriuretic peptide (ANP). We performed experiments in anest hetized, acutely nephrectomized rats 21-28 days after injection of adr iamycin (7-8 mg/kg iv) or 9-14 days after injection of anti-Fx1A antis erum (5 ml/kg ip) (passive Heymann nephritis; PHN) to test whether ext rarenal resistance also occurred. Proteinuria was significantly elevat ed in both models compared with controls before study. ANP infusion (1 mu g.kg(-1).min(-1)) caused arterial pressure to decrease similarly i n control rats, adriamycin-treated rats, and rats with PHN (by 8.2 +/- 1.0, 9.4 +/- 2.3, and 9.0 +/- 2.0%, respectively; all P < 0.05 vs. bo th baseline and vehicle-infused control rats). In control rats, hemato crit increased progressively to a maximal value 9.5 +/- 0.9% over base line as a result of the infusion, an increase corresponding to a reduc tion in plasma volume of 16.1 +/- 0.9%. The ANP-induced increase in he matocrit was preserved in adriamycin-treated rats (9.2 +/- 1.3%) but w as markedly blunted in rats with PHN (2.4 +/- 1.3%; P < 0.0001 vs. ANP infusion in control rats). ANP infusion increased plasma ANP levels t o the same extent in the three groups, whereas plasma guanosine 3',5'- cyclic monophosphate was significantly lower in rats with PHN compared with both control and adriamycin-treated rats. Infusion of a subpress or dose of angiotensin II (ANG II, 2.5 ng.kg(-1).min(-1)) fully restor ed the ANP-induced increase in hematocrit in rats with PHN. This study demonstrates that I) the hemoconcentrating and hypotensive actions of ANP are preserved in adriamycin-treated rats, 2) the effect of ANP on hematocrit and fluid distribution is blunted in rats with PHN while i ts hypotensive action is preserved, and 3) low-level ANG II infusion n ormalizes the hemoconcentrating effect of exogenously infused ANP in r ats with PHN. Thus deficient ANG II generation in rats with PHN, but n ot adriamycin nephrosis, may contribute to extrarenal ANP resistance.