Failure of atrial natriuretic factor to increase with volume expansion in acute and chronic congestive heart failure in the dog.

Abstract

It remains unclear whether the levels of atrial natriuretic factor (ANF) observed in chronic CHF are appropriate for the magnitude of elevations in atrial pressures. Specifically, it is not known whether acute increases in atrial pressure in CHF can result in further significant increases in circulating ANF. The present study was designed to test the hypothesis that in chronic CHF there is an attenuated relation between circulating ANF and atrial pressure such that the heart is unable to respond to further increases in atrial pressure with appropriate increases in ANF. Cardiovascular hemodynamics and plasma levels of ANF were measured at baseline and after rapid right ventricular pacing (RRVP) to produce acute (n = 10, 25 minutes RRVP) and chronic (n=7, 14-16 days RRVP) CHF. Acute saline volume expansion was then performed in each group to determine the response of circulating ANF to acute increases in atrial pressure in both acute and chronic CHF. In chronic CHF, right atrial pressure was much higher than in acute CHF (8.5±0.9 vs. 3.4+1.3 mm Hg, p<0.05); however, circulating ANF was not greater in chronic as compared with acute CHF (385±73 vs. 500±89 pg/ml), which is consistent with an attenuated release of ANF in chronic CHF. In response to volume expansion, right atrial pressure increased in both acute (3.4± 1.3 to 12.1±7 mm Hg) and chronic (8.5 +.9 to 13.3± 1.0 mm Hg) CHF. Despite these marked further increases in atrial pressure, there was no increase in circulating ANF in acute (500±89 to 453±79 pg/ml) or chronic (385±73 to 379±95 pg/ml) CHF. These studies demonstrate maximal release of ANF in acute and chronic CHF that cannot be increased despite further, acute elevations in atrial pressure and is not overcome despite the chronically elevated atrial pressures observed in chronic CHF. (Circulation 1989;80:651-657

Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones

“…A blunted natriuretic response after pharmacological doses of ANP and BNP has been observed in experimental models and in patients with chronic HF, suggesting a resistance to the biological effects of CNHs, principally natriuresis (10,73,100). As discussed in detail previously (11,16), resistance to the biological action of CNHs can be attributed at least to three different causes/mechanisms, acting at prereceptor, receptor, and postreceptor levels, respectively ( Table 3).…”

Cardiorenal actions of neutral endopeptidase inhibition in experimental congestive heart failure.

“…Dogs were then paced for 8 days, which resulted in the clinical signs of CHF. 17,18 The dogs were fasted overnight before the acute experiment and given an oral dose of lithium (300 mg). Before the acute experiment, the dogs were anesthetized with fentanyl (0.005-0.01 mg/kg) and sodium pentobarbital (5-10 mg/kg) given intravenously.…”

Natriuretic peptides in the pathophysiology of congestive heart failure

“…In chronic severe CHF, however, the synthetic capacity of the atria may be overwhelmed relative to the demands of the system, leading to a state of relative deficiency. Indeed, Redfield et al [20] demonstrated in chronic severe experimental CHF an impaired capacity to release ANP in response to acute volume expansion with increases in atrial pressures. Volpe et al [21] have also demonstrated an impaired release of ANP in humans with dilated cardiomyopathy and severe CHF during acute volume expansion.…”