(Circulation. 1999;99:1485-1491.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Aldosterone, Not Estradiol, Is the Physiological Agonist for Rapid Increases in cAMP in Vascular Smooth Muscle Cells
From the Institute of Clinical Pharmacology, Klinikum Mannheim of the University of Heidelberg, Mannheim, Germany.
Correspondence to Martin Wehling, MD, Institute of Clinical Pharmacology, Klinikum Mannheim, Theodor Kutzer Ufer 1-3, D-68135 Mannheim, Germany. E-mail martin.wehling{at}medinn.med.uni-muenchen.de
Background—Steroid-induced gene regulation in the endocrine tissues and vascular wall is achieved through the interaction of specific receptor proteins and promoters of target genes. In addition to these delayed steroid actions, rapid effects of steroids have been reported in various tissues that were clearly incompatible with the classic theory of genomic steroid action.
Methods and Results—Because high doses of 17ß-estradiol have
been shown to modulate intracellular cAMP levels in vascular smooth
muscle cells, steroid-induced stimulation of adenylate
cyclase stimulation and phosphorylation of cAMP
response element binding protein was investigated in porcine
coronary artery vascular smooth muscle cells.
Aldosterone induces a 
1.5- to 2.5-fold increase in
intracellular cAMP levels (EC50 0.01 to 0.1 nmol/L)
within 1 minute, whereas 17ß-estradiol and hydrocortisone act only at
supraphysiological concentrations (10
µmol/L). Aldosterone-induced changes in intracellular
cAMP are calcium dependent; they are not blocked by
inhibitors of mineralocorticoid receptors, transcription,
or protein synthesis. In addition, aldosterone induces a
time-dependent phosphorylation of cAMP response element
binding protein with potential transcriptional importance.
Conclusions—A nongenomic modulation of vascular smooth muscle cells by aldosterone is consistent with the data that aldosterone, not estrogen, is the physiological stimulus for cAMP.
Key Words: vasculature • pharmacology • hormones • muscle, smooth
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