We investigated atrial natriuretic factor (ANF) in humans, measuring plasma immunoreactive (ir) ANF (in femtomoles per milliliter), and renal, hormonal, and hemodynamic responses to ANF infusion, in normal subjects (NL) and congestive heart failure patients (CHF). Plasma irANF was 11±0.9 fmol/ml in NL and 71±9.9 in CHF (P < 0.01); the latter with twofold night ventricular increment (P < 0.05). In NL, ANF infusion of 0.10 ig/ kg per min (40 pmol/kg per min) induced increases (P < 0.05) of absolute (from 160±23 to 725±198 iseq/min) and fractional(1-4%) sodium excretion, urine flow rate (from 10±1.6 to 20±2.6 ml/min), osmolar (from 3.2±0.6 to 6.8±1.2 ml/min) and free water (from 6.8±1.6 to 13.6±1.6 ml/min) clearances, and filtration fraction (from 20±1 to 26±2%). Plasma renin and aldosterone decreased 33% and 40%, respectively (P < 0.01). Systolic blood pressure fell (from 112±3 to 104±5 mmHg, P < 0.05) in seated NL; but in supine NL, the only hemodynamic response was decreased pulmonary wedge pressure (from 11±1 to 7±1 mmHg, P < 0.05). In CHF, ANF induced changes in aldosterone and pulmonary wedge pressure, cardiac index, and systemic vascular resistance (all P < 0.05); however, responses of renin and renal excretion were attenuated. ANF infusion increased hematocrit and serum protein concentration by 5-7% in NL (P < 0.05) but not in CHF.

As the characteristics of sodium and water balance in heart failure remain undefined, we evaluated the hemodynamic, metabolic, and hormonal effects of balanced sodium intake in 10 patients with chronic congestive heart failure. We discontinued diuretics to avoid their confounding influence, and all patients received 1 wk of 10 meq and 100 meq balanced sodium intake and controlled free water. Comparing sodium intake of 10 with 100 meq, the following observations were made. There was weight gain (2.0 kg) and increased sodium excretion (11±3 to 63±15 meq/24 h), unaccompanied by increase of blood volume. Both renin-angiotensin system and sympathetic nervous system activity were greater during the 10 meq diet, and suppressed with the 100 meq sodium diet. For both diets, plasma renin and urinary aldosterone excretion were correlated with urnary sodium excretion (r = -0.768, r = -0.726, respectively; P < 0.005). Systemic hemodynamics were minimally changed with increased sodium intake. However, reversal of vasoconstriction by captopril during the 10 meq diet, and its ineffectiveness during the 100 meq diet, indicated a renin-dependent mechanism in the former, and a renin-independent mechanism in the latter diet. There were two subgroups of response to the 100 meq diet: one group (a = 5) achieved neutral balance, while the second (a = 5) avidly retained sodium and water. Renin-angiotensin system activity was significantly higher in the latter group, and the mechanism for differences in sodium excretion for the subgroups could not be identified by blood volume or hemodynamic parameters. Orthostatic hypotension during tilt was greater during the 10 meq sodium diet, and in all cases, related to ineffective hemodynamic and hormonal compensatory responses.

The purpose of this study was to identify the factor(s) that characterize impaired glomerular filtration rate (GFR) in congestive heart failure (CHF) patients. We studied 34 patients, measuring systemic hemodynamics, vasoactive hormones, and sodium and volume status. Renal plasma flow (para-aminohippurate) and GFR (inulin) were assessed by steady-state clearance techniques. Both linear and multiple regression analyses were performed. Impaired GFR was characterized by reduction of renal blood flow and renal fraction of cardiac output, and by an increase of renal vascular resistance. The correlation between GFR and filtration fraction (r = 0.492, P less than 0.003) indicated that individuals with greatest impairment of GFR had the lowest filtration fraction and increased overall renal vascular resistance, indicating dependence of GFR on afferent, rather than efferent vasoconstriction, under conditions of low renal perfusion. Mean vasoactive hormones and blood volume were increased, but without clear cut correlation with GFR. The greatest impairment of GFR was observed in elderly CHF patients, as renal blood flow and function demonstrated an age-dependent decline, in addition to the adverse effects of CHF. In a multiple regression model, renal blood flow and filtration fraction accounted for 69% and 25%, respectively, of the variability of GFR, with a co-linear influence of age. Thus, we have identified age-related, abnormal renal hemodynamic patterns in CHF, and the fragile nature of GFR in the elderly CHF population.

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