Captopril and ANP: changes in renal hemodynamics, glomerular-ANP receptors and guanylate cyclase activity in rats with heart failure.
To define the renal effects of atrial natriuretic peptide (ANP) in heart failure, we studied rats with heart failure after coronary artery ligation. The rats received either captopril (2 milligrams drinking water) or placebo for 4 weeks. Glomerular filtration rate, renal plasma flow, filtration fraction, urine volume, urinary sodium excretion and the percent fractional excretion of sodium were measured before and after an infusion of ANP (0.3 microgram/kg/min). To determine whether changes in ANP receptor binding and responsiveness occur in heart failure and after captopril treatment, we performed radioreceptor binding studies and measured guanylate cyclase activity. Atrial natriuretic peptide in sham-operated rats decreased mean arterial pressure from 118 +/- 5 to 95 +/- 5 mm Hg (P less than .001), increased urine volume from 0.06 +/- 0.02 to 0.16 +/- 0.05 ml/min/kg (P less than .05), urinary sodium excretion, 14.2 +/- 3.1 to 41.4 +/- 8.9 mu eq/min/kg (P less than .02), filtration fraction from 0.30 +/- 0.03 to 0.40 +/- 0.4 (P less than .05), and the percent fractional excretion of sodium from 0.84 +/- 0.19 to 2.85 +/- 0.61 (P less than .02). Atrial natriuretic peptide in untreated rats with heart failure produced no significant systemic or renal hemodynamic effects. In rats with heart failure treated with captopril, ANP decreased mean arterial pressure from 93 +/- 4 to 86 +/- 4 mm Hg (P less than .05) and increased hematocrit from 50 +/- 2 to 52 +/- 1 (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
R W
RW
Department of Internal Medicine, Veterans Administration Medical Center, Tucson 85723.
Raya
T E
TE
Michael
U
U
Foster
S
S
Meeks
T
T
Goldman
S
S
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D002303:Cardiac Output, Low / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects
D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D002216:Captopril; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor