Mineralocorticoid escape by the kidney but not the heart in experimental asymptomatic left ventricular dysfunction

Lisa C. Costello-Boerrigter, Guido Boerrigter, Gail J. Harty, Alessandro Cataliotti, Margaret May Redfield, John C Jr. Burnett

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)481-488
Number of pages8
JournalHypertension
Volume50
Issue number3
DOIs
StatePublished - Sep 2007

Fingerprint

Mineralocorticoids
Left Ventricular Dysfunction
Desoxycorticosterone
Acetates
Kidney
Sodium
Collagen
Urine
Water
Natriuretic Peptides
Brain Natriuretic Peptide
Atrial Natriuretic Factor
Aldosterone
Healthy Volunteers
Homeostasis
Heart Failure
Hemodynamics
Dogs

Keywords

  • Basic science
  • Experimental models
  • Extracellular matrix
  • Heart failure
  • Kidney physiology/pathophysiology
  • Mineralocorticoids

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Mineralocorticoid escape by the kidney but not the heart in experimental asymptomatic left ventricular dysfunction. / Costello-Boerrigter, Lisa C.; Boerrigter, Guido; Harty, Gail J.; Cataliotti, Alessandro; Redfield, Margaret May; Burnett, John C Jr.

In: Hypertension, Vol. 50, No. 3, 09.2007, p. 481-488.

Research output: Contribution to journalArticle

Costello-Boerrigter, Lisa C. ; Boerrigter, Guido ; Harty, Gail J. ; Cataliotti, Alessandro ; Redfield, Margaret May ; Burnett, John C Jr. / Mineralocorticoid escape by the kidney but not the heart in experimental asymptomatic left ventricular dysfunction. In: Hypertension. 2007 ; Vol. 50, No. 3. pp. 481-488.
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AB - 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.

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