Rapid non-genomic effects of aldosterone on rodent vascular function

T R Uhrenholt, J Schjerning, L E Rasmussen, P B Hansen, R Nørregaard, B L Jensen, O Skøtt

Research output: Contribution to journalReviewResearchpeer-review

Abstract

The main role of aldosterone is to maintain body sodium homeostasis by promoting salt reabsorption in the collecting ducts of the kidney. In the cardiovascular system, aldosterone may be harmful in a number of disease states by inducing fibrosis and vascular dysfunction. The present review describes novel results from several laboratories, which show that aldosterone also has beneficial effects in the cardiovascular system by stimulating the production of nitric oxide (NO) from the endothelium. The effect of aldosterone is seen within minutes, and is not inhibited by blockers of gene transcription, thus pointing to a non-genomic mechanism. Furthermore, this potentially beneficial effect is observed at low physiological concentrations of aldosterone (0.1-10 pm). The effect is mediated by the classical mineralocorticoid receptor, and it involves heat shock protein 90, phosphatidylinositol (PI)-3 kinase, protein kinase B, endothelial nitric oxide synthase, and liberation of NO. It is proposed that in healthy individuals with a functioning NO system, the detrimental effects of aldosterone on cardiovascular function are balanced by activation of the potentially beneficial effect of NO. However, in situations with endothelial dysfunction, such as congestive heart failure and hypertension, the negative effects of aldosterone are unopposed and inhibition of aldosterone is warranted.

Original languageEnglish
JournalActa Physiologica Scandinavica
Volume181
Issue number4
Pages (from-to)415-9
Number of pages5
ISSN0001-6772
DOIs
Publication statusPublished - Aug 2004

Fingerprint

Aldosterone
Rodentia
Nitric Oxide
Collecting Kidney Tubules
HSP90 Heat-Shock Proteins
Mineralocorticoid Receptors
Endothelium
Homeostasis
Salts

Keywords

  • Aldosterone
  • Animals
  • Cardiovascular Diseases
  • Endothelium, Vascular
  • Humans
  • Muscle, Smooth, Vascular
  • Rats
  • Receptors, Mineralocorticoid
  • Vasoconstriction
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Review

Cite this

Uhrenholt, T R ; Schjerning, J ; Rasmussen, L E ; Hansen, P B ; Nørregaard, R ; Jensen, B L ; Skøtt, O. / Rapid non-genomic effects of aldosterone on rodent vascular function. In: Acta Physiologica Scandinavica. 2004 ; Vol. 181, No. 4. pp. 415-9.
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Rapid non-genomic effects of aldosterone on rodent vascular function. / Uhrenholt, T R; Schjerning, J; Rasmussen, L E; Hansen, P B; Nørregaard, R; Jensen, B L; Skøtt, O.

In: Acta Physiologica Scandinavica, Vol. 181, No. 4, 08.2004, p. 415-9.

Research output: Contribution to journalReviewResearchpeer-review

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T1 - Rapid non-genomic effects of aldosterone on rodent vascular function

AU - Uhrenholt, T R

AU - Schjerning, J

AU - Rasmussen, L E

AU - Hansen, P B

AU - Nørregaard, R

AU - Jensen, B L

AU - Skøtt, O

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AB - The main role of aldosterone is to maintain body sodium homeostasis by promoting salt reabsorption in the collecting ducts of the kidney. In the cardiovascular system, aldosterone may be harmful in a number of disease states by inducing fibrosis and vascular dysfunction. The present review describes novel results from several laboratories, which show that aldosterone also has beneficial effects in the cardiovascular system by stimulating the production of nitric oxide (NO) from the endothelium. The effect of aldosterone is seen within minutes, and is not inhibited by blockers of gene transcription, thus pointing to a non-genomic mechanism. Furthermore, this potentially beneficial effect is observed at low physiological concentrations of aldosterone (0.1-10 pm). The effect is mediated by the classical mineralocorticoid receptor, and it involves heat shock protein 90, phosphatidylinositol (PI)-3 kinase, protein kinase B, endothelial nitric oxide synthase, and liberation of NO. It is proposed that in healthy individuals with a functioning NO system, the detrimental effects of aldosterone on cardiovascular function are balanced by activation of the potentially beneficial effect of NO. However, in situations with endothelial dysfunction, such as congestive heart failure and hypertension, the negative effects of aldosterone are unopposed and inhibition of aldosterone is warranted.

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KW - Cardiovascular Diseases

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KW - Muscle, Smooth, Vascular

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KW - Vasoconstriction

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