Captopril enhances renal responsiveness to ANF in dogs with compensated high-output heart failure.
The systemic hemodynamic, hormonal, and renal effects of chronic angiotensin-converting enzyme inhibition (CEI) with captopril and the responses to synthetic atrial natriuretic factor (ANF) infusions in the presence and absence of captopril were examined in normal dogs (n = 6) and in dogs with an arteriovenous (AV) fistula and compensated high-output heart failure (n = 6). This experimental model is characterized by normalization of the circulating renin-angiotensin-aldosterone system (RAAS) and persistent elevations in central filling pressures and plasma ANF. In both normal and AV-fistula dogs, oral captopril for 1 wk at 35 mg.kg-1.day-1 in three divided doses produced progressive reductions in arterial and atrial pressures (P less than 0.05), plasma ANF (P less than 0.05), and aldosterone (P less than 0.05). After 1-2 days of a modest increase in urinary sodium excretion (UNaV) (P less than 0.05), all of the dogs regained and maintained sodium balance during captopril administration. On the 8th day of the captopril regimen, synthetic ANF was infused at 15 and 30 ng.kg-1.min-1 for 75-min periods each. Control infusion experiments were performed in the same animals before captopril administration. The normal dogs exhibited dose-related elevations in UNaV (P less than 0.05) that were not augmented with captopril (P greater than 0.05). In contrast, in the AV-fistula dogs the observed renal unresponsiveness to synthetic ANF in the control experiments was reversed with chronic CEI, and ANF-induced UNaV achieved levels comparable to those obtained in the normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Villarreal
D
D
Department of Physiology, University of Missouri School of Medicine, Columbia 65212.
Freeman
R H
RH
Johnson
R A
RA
D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001164:Arteriovenous Fistula / Q000503:physiopathology*; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D016534:Cardiac Output, High / Q000503:physiopathology*; D006152:Cyclic GMP / Q000652:urine; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007262:Infusions, Intravenous; D009318:Natriuresis / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000187:drug effects*
D011994:Recombinant Proteins; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D002216:Captopril; D006152:Cyclic GMP