GLOMERULAR ATRIAL-NATRIURETIC-FACTOR RECEPTORS IN EXPERIMENTAL CONGESTIVE-HEART-FAILURE

Heart failure is usually characterized by a relative insensitivity to atrial natriuretic factor (ANF). Downregulation of ANF receptors has b een reported but remains controversial. Renal response to ANF infusion , glomerular ANF receptors, and guanosine 3',5'-cyclic monophosphate ( cGMP) production have been studied in rabbits with congestive heart fa ilure (CHF) after traumatic aortic regurgitation and abdominal aortic stenosis. Diuresis and natriuresis induced by ANF infusions were signi ficantly decreased in CHF animals. Plasma cGMP was higher in CHF rabbi ts before ANF administration than in controls (37.6 +/- 7.2 vs. 17.1 /- 3.9 pmol/ml, P < 0.02) and increased to a same level after ANF in b oth groups (48.8 +/- 4.2 vs. 52.5 +/- 2.8 pmol/ml, NS). No difference was found in glomerular ANF receptor density (436 +/- 54 vs. 425 +/- 5 7 fmol/mg protein, NS) nor in affinity between the two groups (dissoci ation constant: 240 +/- 24 vs. 347 +/- 49 pM, NS). Moreover, in vitro glomerular cGMP production in response to exogenous ANF was preserved. In conclusion, despite a blunted renal response to ANF in vivo, glome rular ANF receptors were unchanged in this model, and no defect in cGM P production in response to ANF was found. This suggests the existence of an intracellular defect beyond the second messenger.