DOCA administration and atrial natriuretic factor in dogs with chronic heart failure

The chronic reserve for the secretion of atrial natriuretic factor (ANF) was studied in conscious dogs with an arteriovenous (a-v) fistula, a model of high-output heart failure. After the first 7 days of marked sodium retention after creation of the a-v fistula, the animals regained sodium balance for the subsequent 3 wk. This compensatory natriuresis occurred in the presence of significant increases in right atrial pressure and was associated with marked and sustained elevations in plasma ANF and with the return of plasma renin and aldosterone to base-line values. The cardiac reserve for ANF secretion was further evaluated in these dogs with compensated high-output heart failure during additional progressive elevations in cardiac filling pressures induced by 3 wk of deoxycorticosterone acetate (DOCA) administration. During the DOCA regimen, plasma ANF increased an additional twofold from its high base line. Arterial blood pressure increased by 6-12 mmHg, and plasma renin activity was suppressed. However, the animals consistently retained sodium, and the high plasma levels of ANF were unable to counterbalance the sodium-retaining actions of DOCA. After termination of DOCA, the dogs exhibited a marked natriuresis, and all the hemodynamic and hormonal parameters returned to pre-DOCA control levels. This longitudinal study demonstrates that the cardiac reserve for chronic ANF secretion is well maintained in dogs with an a-v fistula during progressive cardiac volume overload. The present results suggest that the ANF endocrine system may represent one chronic compensatory mechanism to achieve sodium balance in heart failure when there is concomitant normalization of the renin-aldosterone system. Finally, the failure of the a-v fistula dogs to escape from the sodium-retaining actions of DOCA is not related to a deficiency in the secretion of ANF.