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 been 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 failure (CHF) after traumatic aortic regurgitation and abdominal aortic stenosis. Diuresis and natriuresis induced by ANF infusions were significantly decreased in CHF animals. Plasma cGMP was higher in CHF rabbits 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 both 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 +/- 57 fmol/mg protein, NS) nor in affinity between the two groups (dissociation 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, glomerular ANF receptors were unchanged in this model, and no defect in cGMP production in response to ANF was found. This suggests the existence of an intracellular defect beyond the second messenger.
Isnard
R
R
Service de Cardiologie, Hôpital Pitié-Salpétrière, Paris, France.
Carayon
A
A
Eurin
J
J
Maistre
G
G
Bouanani
N
N
Barthelemy
C
C
Crozatier
B
B
Komajda
M
M
Legrand
J C
JC
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology; D001667:Binding, Competitive; D006152:Cyclic GMP / Q000097:blood / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D007678:Kidney Glomerulus / Q000378:metabolism*; D011817:Rabbits; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*
D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP