title: Mineralocorticoid escape by the kidney but not the heart in experimental asymptomatic left ventricular dysfunction.
abstract: Unlike healthy subjects, overt congestive heart failure cannot "escape" the sodium- and water-retaining actions of mineralocorticoid excess. It is undefined whether escape occurs in asymptomatic left ventricular dysfunction (ALVD), which is characterized by preserved sodium homeostasis, natriuretic peptide activation, and normal circulating aldosterone. We hypothesized that, in ALVD, mineralocorticoid excess with exogenous deoxycorticosterone acetate (DOCA) would overwhelm renal compensatory mechanisms, resulting in sodium and water retention, and promote renal and cardiac collagen deposition. ALVD was induced in 2 groups (N=5 each) of dogs by tachypacing at 180 bpm. Urine was collected daily and blood drawn at baseline and days 2, 5, 8, and 11. One group served as control (ALVD), and the other received DOCA (ALVD+DOCA) starting at day 2 of pacing. Urine flow and sodium excretion were unchanged in the ALVD group. In ALVD+DOCA, urine flow and sodium excretion decreased on the first 2 days DOCA was given but normalized starting day 4. Urine flow and urinary cGMP excretion increased in ALVD+DOCA after DOCA escape. Plasma atrial natriuretic peptide, B-type natriuretic peptide, and cGMP increased equally in both groups. There were no differences in cardiorenal and hemodynamic parameters in an acute study on day 11. Although renal collagen area fraction was similar, left ventricular collagen area fraction in ALVD+DOCA was significantly higher than in ALVD (3.3+/-0.4% versus 2.0+/-0.2%; P=0.012). We conclude that ALVD can escape the sodium- and water-retaining effects of mineralocorticoid excess. Despite renal escape, increased left ventricular collagen deposition suggests that the heart but not the kidney failed to escape the tissue effects of DOCA.
authors.affiliation: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, USA. Costello.Lisa@mayo.edu
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Costello-Boerrigter
authors.forename: Guido
authors.initials: G
authors.lastname: Boerrigter
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Harty
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cataliotti
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000818:Animals; D001834:Body Water / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D006152:Cyclic GMP / Q000652:urine; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004231:Diuresis; D004285:Dogs; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009318:Natriuresis; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism* / Q000652:urine
chemical_list: D018161:Receptors, Mineralocorticoid; D003900:Desoxycorticosterone; D003094:Collagen; D012964:Sodium; D006152:Cyclic GMP