DIVERGENT REGULATION OF ATRIAL-NATRIURETIC-FACTOR RECEPTORS IN HIGH-OUTPUT HEART-FAILURE

We have investigated whether binding parameters and subtypes of glomerular, papillary, and vascular atrial natriuretic factor (ANF) receptors differ in rats with moderate high-output heart failure [aortocaval (AC) shunt] from their sham-operated controls. Body weight was lower and relative heart weight was higher in the AC shunt group than in the control group. Plasma renin activity (PRA) was also greater in AC shunt rats. Plasma COOH- and NH2-terminal ANF levels were higher in AC shunt animals than in their control counterparts. Total atrial ANF content was elevated in both the right and left atria of the AC shunt group. Glomerular and papillary ANF receptor density (B(max)) and ANF receptor affinity (K(d)) were similar in both AC shunt and control rats. Vascular ANF receptor density and affinity were lower in AC shunt (B(max) = 65 +/- 13 fmol . mg protein; K(d) = 467 +/- 52 pM) than in control rats (B(max) = 188 +/- 34 fmol . mg protein; K(d) = 278 +/- 11 pM). Irreversible cross-linking of I-125-labeled ANF followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions and radioautography demonstrated that both high- and low-molecular weight receptors were unchanged in glomerular membranes and downregulated in vascular membranes from AC shunt animals. However, guanosine 3',5'-cyclic monophosphate (cGMP) production by the isolated glomeruli of AC shunt rats was lower than that of controls. We conclude that in the presence of elevated plasma ANF levels, glomerular, papillary, and vascular ANF receptors may be regulated differently.