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, which binds specifically to ANFR-C. The present studies were undertaken to determine total metabolic (TMCR), pulmonary (PCR), and renal clearance rates (RCR) of ANF in a group of seven mongrel dogs in chronic congestive heart failure (CHF) in comparison with a control group (n = 6). TMCR was not altered in CHF [1,534 +/- 319 vs. control: 1,735 +/- 208 ml/min; P = not significant (NS)] in association with an elevation of 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 similarly (CHF: 753 +/- 134 vs. control: 972 +/- 156 ml/min; P = NS). PCR was lower in CHF (286 +/- 431 vs. 1,672 +/- 407 ml/min; P < 0.05), whereas 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 elevated endogenous ANF in CHF; 2) total functional activity of the clearance 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.
Brandt
R R
RR
Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Redfield
M M
MM
Aarhus
L L
LL
Lewicki
J A
JA
Burnett
J C
JC
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D004231:Diuresis; D004285:Dogs; D006333:Heart Failure / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D009318:Natriuresis; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*
D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor