Hypertension, Vol 20, 67-73, Copyright © 1992 by American Heart Association
ME Ullian, JR Schelling and SL Linas
Clinical states in which angiotensin II is increased are often associated
with increases in mineralocorticoids. To determine the effects of
mineralocorticoids on angiotensin II action, we examined the effects of
aldosterone on angiotensin II receptor expression and function in cultured
rat vascular smooth muscle cells. Incubation with aldosterone resulted in
concentration- and time-dependent increases in angiotensin II receptor
number, without changes in binding affinity. For example, incubation with 1
microM aldosterone for 40 hours resulted in 59% increases in angiotensin II
receptor number. Increases in angiotensin II receptors were dependent on
protein synthesis as evidenced by the time dependency of upregulation and
inhibition by cycloheximide. Incubation with aldosterone resulted in
enhanced angiotensin II-stimulated phospholipase C activation, as
demonstrated by increases in angiotensin II-induced inositol phosphate
responses in proportion to the increases in receptor number. In addition,
aldosterone prevented angiotensin II-induced downregulation of angiotensin
II surface receptors and angiotensin II desensitization of inositol
phosphate formation. In summary, aldosterone 1) directly increased
angiotensin II receptor number, 2) increased angiotensin II- stimulated
inositol phosphate responses, and 3) prevented angiotensin II-induced
downregulation and desensitization. In conclusion, aldosterone may
potentiate the pressor responses of angiotensin II via effects on
angiotensin II receptors.
ARTICLES
Aldosterone enhances angiotensin II receptor binding and inositol phosphate responses
Medical University of South Carolina, Charleston.
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