CLEARANCE RECEPTOR-MEDIATED CONTROL OF ATRIAL-NATRIURETIC-FACTOR IN EXPERIMENTAL CONGESTIVE-HEART-FAILURE

Circulating atrial natriuretic factor (ANF) is regulated by clearance receptors (ANFR-C). C-ANF-(4-23) is a ring-deleted analogue of ANF, wh ich binds specifically to ANFR-C. The present studies were undertaken to determine total metabolic (TMCR), pulmonary (PCR), and renal cleara nce rates (RCR) of ANF in a group of seven mongrel dogs in chronic con gestive heart failure (CHF) in comparison with a control group (n = 6) . TMCR was not altered in CHF [1,534 +/- 319 vs. control: 1,735 +/- 20 8 ml/min; P = not significant (NS)] in association with an elevation o f circulating endogenous ANF (206 +/- 44 vs. control: 36 +/- 10 pg/ml; P < 0.01). Infusion of C-ANF-(4-23) reduced TMCR in both groups simil arly (CHF: 753 +/- 134 vs. control: 972 +/- 156 ml/min; P = NS). PCR w as lower in CHF (286 +/- 431 vs. 1,672 +/- 407 ml/min; P < 0.05), wher eas RCR was not different (10 +/- 24 vs. control: 15 +/- 25 ml/min; P = NS). ANFR-C blockade did not facilitate urinary sodium excretion in CHF. These studies demonstrate that 1) TMCR does not contribute to ele vated endogenous ANF in CHF; 2) total functional activity of the clear ance receptor pathway is preserved in CHF; and 3) renal ANF metabolism and the clearance receptor pathway are not linked to the avid sodium retention and renal ANF resistance observed in chronic CHF.