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Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
P-glycoprotein modulates aldosterone plasma disposition and tissue uptake
Robert B Parker1, C Ryan Yates, S Casey Laizure
1University of Tennessee Health Science Center, Department of Pharmacy, Memphis, TN 38163, USA. rparker@utmem.edu
Journal of Cardiovascular Pharmacology
|January 21, 2006
Summary
P-glycoprotein (P-gp) limits aldosterone uptake in the brain and heart. P-gp deficiency increases aldosterone levels in these organs, suggesting a key role in cardiovascular health.
Area of Science:
- Endocrinology
- Cardiovascular Physiology
- Pharmacology
Background:
- Aldosterone is crucial in cardiovascular diseases like heart failure and hypertension.
- Aldosterone's effects are mediated by the mineralocorticoid receptor.
- Cellular uptake and distribution influence aldosterone activity.
Purpose of the Study:
- To investigate if P-glycoprotein (P-gp) affects aldosterone uptake in the brain and heart.
- To compare aldosterone distribution in wild-type and P-gp-deficient mice.
Main Methods:
- Utilized [3H]-aldosterone to track distribution in wild-type and mdr1a/1b (-/-) mice.
- Measured plasma and tissue concentrations of [3H]-aldosterone.
- Analyzed the area under the concentration-time curves.
Main Results:
- P-gp-deficient mice showed significantly higher [3H]-aldosterone levels in plasma, brain, and heart.
- Area under the curve was 2.0-fold higher in the brain and 1.6-fold higher in the heart and plasma of deficient mice.
- P-gp modestly limits aldosterone uptake into the brain.
Conclusions:
- P-glycoprotein plays a significant role in aldosterone's plasma disposition.
- P-gp limits aldosterone uptake into the brain and potentially the heart.
- P-gp may be a key regulator of aldosterone's effects in target organs.
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