Zinc dyshomeostasis in rats with aldosteronism. Response to spironolactone

Manesh Thomas, Alex Vidal, Syamal Bhattacharya, Robert A. Ahokas, Yao Sun, Ivan Gerling, Karl Weber

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Zinc is a structural constituent of many proteins, including Cu/Zn superoxide dismutase (SOD), an endogenous antioxidant enzyme. Hypozincemia has been found in patients hospitalized with congestive heart failure, where neurohormonal activation, including the renin-angiotensin-aldosterone system (RAAS), is expected and oxidative stress is present. This study was undertaken to elucidate potential pathophysiological mechanisms involved in Zn dyshomeostasis in aldosteronism. In rats receiving aldosterone/salt treatment (ALDOST) alone for 1 and 4 wk or in combination with spironolactone (Spiro), an ALDO receptor antagonist, we monitored 24-h urinary and fecal Zn excretion and tissue Zn levels in heart, liver, and skeletal muscle, together with tissue metallothionein (MT)-I, a Zn2+-binding protein, and Cu/Zn-SOD activities in plasma and tissues. When compared with unoperated, untreated, age-/sex-matched controls, urinary and, in particular, fecal Zn losses were markedly increased (P < 0.05) at days 7 and 28 of ALDOST, leading to hypozincemia and a fall (P < 0.05) in plasma Cu/Zn-SOD activity. Microscopic scars and perivascular fibrosis of intramural coronary arteries first appeared in the right and left ventricles at week 4 of ALDOST and were accompanied by increased (P < 0.05) tissue Zn, MT-I, and Cu/Zn-SOD activity, which were not found in uninjured liver or skeletal muscle. Spiro cotreatment prevented cardiac injury and Zn redistribution to the heart. Thus increased urinary and fecal Zn losses, together with their preferential translocation to sites of cardiac injury, where MT-I overexpression and increased Cu/Zn-SOD activity appeared, contribute to Zn dyshomeostasis in rats with aldosteronism, which were each prevented by Spiro. These findings may shed light on Zn dyshomeostasis found in patients with decompensated heart failure.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number4
DOIs
StatePublished - Oct 1 2007

Fingerprint

Spironolactone
Hyperaldosteronism
Zinc
Metallothionein
Aldosterone
Salts
Heart Ventricles
Skeletal Muscle
Heart Failure
Liver
Wounds and Injuries
Renin-Angiotensin System
Cicatrix
Coronary Vessels
Myocardium
Carrier Proteins
Oxidative Stress
Fibrosis
Therapeutics
Antioxidants

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Zinc dyshomeostasis in rats with aldosteronism. Response to spironolactone. / Thomas, Manesh; Vidal, Alex; Bhattacharya, Syamal; Ahokas, Robert A.; Sun, Yao; Gerling, Ivan; Weber, Karl.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 293, No. 4, 01.10.2007.

Research output: Contribution to journalArticle

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