Role of endogenous atrial natriuretic peptide on systemic and renal hemodynamics in heart failure rats.
To investigate the role of endogenous atrial natriuretic peptide (ANP) in rats with heart failure (HF), we administered HS-142-1 (HS; 3 mg/kg body wt iv), a novel nonpeptide ANP-receptor antagonist, to rats with surgically induced myocardial infarction and sham-operated rats. HF was characterized by a higher left ventricular end-diastolic pressure and higher plasma ANP concentration vs. controls. HS administration significantly reduced the plasma and urinary levels of guanosine 3',5'-cyclic monophosphate in rats with HF [plasma concentration 10.6 +/- 2.6 vs. 2.7 +/- 0.4 nM (P < 0.05); urinary excretion 48 +/- 8 vs. 12 +/- 2 pmol/min (P < 0.05)]. Systemic and renal hemodynamics were unaffected by HS administration. Urine flow (-35%) and urinary sodium excretion (-50%) were significantly decreased after HS only in those rats with HF that had no changes in systemic and renal hemodynamics. These results suggest that the elevated ANP levels in HF do not contribute directly to the maintenance of systemic hemodynamics but rather compensate for the HF mainly via diuresis and natriuresis, achieved by the inhibition of renal tubular reabsorption rather than by renal vasodilatation.
Nishikimi
T
T
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Miura
K
K
Minamino
N
N
Takeuchi
K
K
Takeda
T
T
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D002303:Cardiac Output, Low / Q000097:blood / Q000503:physiopathology*; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011134:Polysaccharides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D012083:Renin / Q000097:blood
C072551:HS 142-1; D011134:Polysaccharides; D009320:Atrial Natriuretic Factor; D012083:Renin; D006152:Cyclic GMP