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3Department of Pharmacology, University of Heidelberg, Heidelberg; 2Endocrine Practice, Heidelberg; 4Medical Research Center, University of Heidelberg, Mannheim; and 1Department of Cardiovascular Medicine, University of Greifswald, Greifswald, Germany
Submitted 19 September 2005 ; accepted in final form 19 July 2006
ANG II and potassium are known to increase steroidogenic acute regulatory protein (StAR) levels. However, a corresponding increase in StAR mRNA levels has so far been observed only in response to ANG II. We therefore studied the regulation of adrenal StAR mRNA expression in the context of dietary potassium-stimulated aldosterone production. Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were fed a diet containing either 1 or 4% KCl for 5 days. The high-potassium diet increased StAR mRNA levels within the zona glomerulosa in both strains, as demonstrated by in situ hybridization. However, aldosterone production increased in WKY but not in SHR (WKY: from 22.8 ± 4.8 to 137 ± 25 ng/100 ml, P < 0.001, vs. SHR: from 29 ± 3.8 to 51 ± 10.2 ng/100 ml, not significant). This increase was associated with an increase in Cyp11b2 mRNA levels in WKY (3-fold; P < 0.001) but not in SHR. In both strains, the 4% KCl diet was associated with increased plasma renin-independent aldosterone production, as indicated by the marked increase of the aldosterone-to-renin ratios (from 1.4 ± 0.3 to 9 ± 3 in WKY and from 3 ± 1 to 14 ± 5 in SHR; P < 0.002). We conclude that an increase of StAR mRNA levels within the outer cortex is involved in the long-term adrenal response to potassium. This increase alone is not sufficient to increase aldosterone production in the presence of normal Cyp11b2 mRNA levels.
Cyp11b2; zona glomerulosa; steroidogenic acute regulatory protein
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