Regional distribution of the cardiac output and renal responses to atrial natriuretic peptide infusion in rabbits with congestive heart failure.
1. A biventricular, low-output congestive cardiomyopathy was induced in 19 rabbits by administering adriamycin (16 mg/kg). The effects of alpha-rat atrial natriuretic peptide (ANP) infused at 0.1, 0.2 and 0.4 micrograms/kg per min, were then examined in terms of (i) central haemodynamics (ii) regional blood flow (iii) renal function and (iv) plasma norepinephrine and plasma renin. 2. In this dose range, ANP produced progressive and significant falls in stroke volume, cardiac output and mean arterial pressure, owing to a fall in venous return. The heart rate response to this was blunted. 3. Using radiolabelled microspheres, significant falls in the perfusion of cutaneous, gastrointestinal and musculoskeletal tissues were observed, due to reduced vascular conductances in these beds. These changes were accompanied by activation of the sympathetic nervous system as evidenced by a progressive rise in plasma norepinephrine. A significant increase in plasma renin was only observed with the highest infusion of ANP. 4. Renal blood flow was maintained in the face of a falling mean arterial pressure and cardiac output, but diuretic and natriuretic effects were absent. 5. It was concluded that the dominant influence of ANP infusion in this model of heart failure appeared to be a reduction in cardiac preload with detrimental overall haemodynamic consequences.
Langton
D
D
Monash University Department of Medicine, Monash Medical Centre, Melbourne, Victoria, Australia.
Jover
B F
BF
Trigg
L
L
Fullerton
M
M
Blake
D W
DW
McGrath
B P
BP
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001826:Body Fluids / Q000187:drug effects / Q000378:metabolism; D002302:Cardiac Output / Q000187:drug effects*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000503:physiopathology; D004317:Doxorubicin / Q000494:pharmacology; D006333:Heart Failure / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011817:Rabbits; D012083:Renin / Q000097:blood
D004317:Doxorubicin; D009320:Atrial Natriuretic Factor; D012083:Renin; D009638:Norepinephrine