ROLE OF ATRIAL-NATRIURETIC-FACTOR IN IMPAIRED SODIUM-EXCRETION OF NORMOCAPNIC AND HYPERCAPNIC PATIENTS WITH CHRONIC OBSTRUCTIVE LUNG-DISEASE

To investigate the mechanisms of sodium retention in patients with chronic obstructive lung disease (COLD), we examined the renal and hormonal responses to volume expansion with isotonic saline and to infusion of atrial natriuretic factor (ANF) in 10 hypercapnic (Pa(CO2) 52 +/- 2 mm Hg) and 12 normocapnic patients (Pa(CO2) 39 +/- 1 mm Hg). Sodium excreted within 4 h of loading (expressed as % sodium load) was 23.5 +/- 2.5% (p < 0.05) in normocapnic and 8.5 +/- 1.5% (p < 0.001) in hypercapnic patients, compared with 32.5 +/- 3.0% in 11 age-matched control subjects. Sodium excretion and renal blood flow correlated negatively with arterial P(CO2) and positively with FEV1. Basal plasma ANF concentrations were 72 +/- 5 pg/ml in controls, 100 +/- 14 pg/ml in normocapnic patients, and 230 +/- 52 pg/ml in hypercapnic patients (p < 0.001). Plasma renin activity and aldosterone did not differ between groups. In response to volume expansion, plasma ANF increased in both normocapnic and controls (with a greater increase in normocapnic patients) but remained unchanged in hypercapnic patients. Exogenous ANF increased glomerular filtration rate, renal plasma flow, natriuresis, and diuresis in both groups of patients. Patients with COLD have depressed renal function that appears unrelated to activation of the renin-angiotensin-aldosterone system. An increased secretory response of ANF to volume expansion may help to maintain volume homeostasis in normocapnic patients, while a blunted secretory response of ANF may contribute to sodium retention in hypercapnic patients.