Rapid non-genomic effects of aldosterone on rodent vascular function.
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.
Uhrenholt
T R
TR
Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark.
Schjerning
J
J
Rasmussen
L E
LE
Hansen
P B
PB
Nørregaard
R
R
Jensen
B L
BL
Skøtt
O
O
D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D051381:Rats; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*
D018161:Receptors, Mineralocorticoid; D000450:Aldosterone