Restoration of renal response to atrial natriuretic factor in experimental low-output heart failure.
The renal response to atrial natriuretic factor (ANF) has been shown to be blunted in several experimental models of acute and chronic congestive heart failure. The mechanism responsible for this blunted response has been postulated to be activation of the renin-angiotensin system with associated potent antinatriuretic effects and/or the reduction in renal perfusion pressure (RPP) characteristic of heart failure. The present study was designed to examine the relative role of these two factors in mediating the blunted response to ANF in a model of acute low output heart failure produced by thoracic inferior vena cava constriction (TIVCC) in the anesthetized dog. TIVCC was produced in five groups of dogs. In group 1, ANF was infused after TIVCC to document the blunted natriuretic response. In group 2, ANF was infused after TIVCC in the presence of blockade of intrarenal angiotensin II (ANG II) by the intrarenal infusion of saralasin (Sar) at a dose without systemic effects. In group 3, ANF was infused after TIVCC in the presence of restoration of RPP by infusion of ANG II at a dose titrated to restore RPP to the level present before TIVCC. In group 4, ANF was infused in the presence of restoration of RPP with ANG II and blockade of intrarenal ANG II with Sar. Group 5 served as an additional control group where the effect of ANG II and Sar in TIVCC was examined in the absence of ANF. Restoration of RPP but not blockade of intrarenal ANG II resulted in a restoration of the response of sodium excretion and glomerular filtration rate to ANF. ANG II plus Sar in the absence of ANF did not produce a natriuresis. We conclude that RPP, more than intrarenal ANG II, modulates the blunted renal response to ANF observed in this model of acute low-output heart failure.
Redfield
M M
MM
Department of Internal Medicine, Mayo Medical School, Rochester, Minnesota 55905.
Edwards
B S
BS
Heublein
D M
DM
Burnett
J C
JC
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure; D002302:Cardiac Output; D002303:Cardiac Output, Low / Q000503:physiopathology*; D004285:Dogs; D005919:Glomerular Filtration Rate; D006439:Hemodynamics; D007668:Kidney / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D012079:Renal Circulation; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000494:pharmacology; D014655:Vascular Resistance; D014682:Vena Cava, Inferior / Q000502:physiology
D009320:Atrial Natriuretic Factor; D012083:Renin; D012504:Saralasin