Role of Atrial-natriuretic-peptide In the Pathogenesis of Sodium Retention In Iddm With and Without Glomerular Hyperfiltration

The pathogenetic determinants of sodium retention in IDDM are not fully understood. The alm of this study was to elucidate the action of ANP in 11 IDDM patients with high GFR (greater-than-or-equal-to 135 ml . min-1 . 1.73 m-2) , referred to here as HF patients; in 10 IDDM patients with normal GFR (>90 and <135 ml . min-1 . 1.73 m-2) , referred to here as NF patients; and 12 control subjects, here called C subjects, at baseline and during saline infusion administered on the basis of either body weight (2 mmol . kg-1 . 60 min-1; Saline 1) or of ECV (12 mM . ECVL-1 . 90 min-1; Saline 2) during euglycemic insulin-glucose clamp. C subjects and both HF and NF IDDM patients received a second Saline 1 infusion accompanied by ANP infusion (0.02-mu-g . kg-1 . min-1) at euglycemic levels. HF and NF patients were studied again after 3 mo of treatment with (10 mg/day). Quinapril (CI 906, Malesci, Florence, Italy), an ACE inhibitor without sulfydryl group. At baseline, both HF and NF IDDM patients had higher plasma ANP concentrations than C subjects (HF, 36 +/- 4, P < 0.01 and NF, 34 +/- 3, P < 0.01 vs. C, 19 +/- 3 pg/ml). Plasma ANP and natriuretic response to isotonic volume expansion was impaired both in HF (44 +/- 8 pg/ml, NS vs. base) and NF (40 +/- 7 pg/ml, NS vs. base) compared with C (41 +/- 4 pg/ml, P < 0.01 vs. base) during Saline 1. On the contrary, plasma ANP response to Saline 2 was similar in HF and NF patients and C subjects, but IDDM patients had still lower urinary sodium excretion rates. The simultaneous administration of ANP and Saline 1 resulted in comparable plasma ANP plateaus in C subjects and HF and NF patients. However, urinary sodium excretion rate was significantly lower in HF and NF patients than in C subjects: HF, 267 +/- 64, P < 0.01 and NF, 281 +/- 42, P < 0.01 vs. C, 424 +/- 39-mu-mol . min-1 . 1.73 m-2 . During simultaneous administration of ANP and Saline 1, GFR and FF increased in C subjects, but not in HF and NF patients. HF and NF patients had higher urinary vasodilatory prostanoid excretion rates than C subjects at baseline. Saline infusion did not change urinary excretion rate of prostanoids either in C subjects or IDDM patients (both NF and HF). Quinapril significantly decreased baseline plasma ANP concentrations in both HF and NF, near normalized ANP response to Saline 1, and increased sodium excretion rate both during Saline 1 and 2, without any change in GFR and urinary prostanoid excretion rates. The results of thia study suggest that in IDDM patients with high or normal GFR, 1) natriuresis is impaired during saline infusion, even when ANP levels are normal, suggesting the presence of resistance to ANP action, 2) ANP release is normal if volume expansion la proportionate to ECV magnitude, 3) urinary excretion rate of vasodilatory prostanoids is high, and 4) ACE inhibitors ameliorate natriuretic and ANP response to saline infusion. These findings suggest that a resistance to the natriuretic action of ANP, and possibly of vasodilatory prostanoids, contribute to sodium retention in IDDM, irrespective of glomerular hyperfiltration.