Influence of captopril on adrenal cytochrome P-450s and adrenodoxin expression in high potassium or low sodium intake.
To investigate the role of the renin-angiotensin system in steroidogenic enzyme expression, the angiotensin-I converting enzyme inhibitor captopril was administered in conjunction with high potassium (K+) or low (Na+) intake to rats for a 7-day period. Northern blot analysis of adrenocortical zona glomerulosa RNA revealed that sodium restriction markedly increased mRNA production of P-450scc (3.1-fold) and P-450(11 beta) (3.4-fold) as well as of the electron donor adrenodoxin (2.0-fold). Captopril combined to the low Na+ diet led to suppression of these effects and, as also seen with captopril alone, further diminished P-450(11 beta) mRNA levels below controls. These responses were accompanied by parallel changes in respective protein levels of the enzymes as indicated by Western blot analyses. Captopril was also shown to inhibit the K(+)-stimulated levels of P-450(11 beta) mRNA (3.3-fold) and protein (1.4-fold) beneath control values (0.6- and 0.8-fold, respectively). On the other hand, increased P-450scc mRNA and protein levels by K+ loading were not affected by captopril treatment. No response was observed in any steroidogenic enzyme expression in zona fasciculata-reticularis following either diet with or without captopril. Thus, the inhibitory effect of captopril on stimulated steroidogenesis seemed to be mediated in part through transcriptional regulation of P450s. In addition, it appeared that P-450(11 beta) expression might be under the control of the renin-angiotensin system in both high K+ and low Na+ diets as opposed to the K+ stimulation of P-450scc where other mechanisms seemed to be involved.
Department of Biochemistry, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
A
A
Tremblay
J G
JG
Lehoux
D000302:Adrenal Cortex / Q000187:drug effects / Q000502:physiology*; D000325:Adrenodoxin / Q000096:biosynthesis / Q000235:genetics*; D000450:Aldosterone / Q000097:blood; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002216:Captopril / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D015342:DNA Probes; D015870:Gene Expression / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012084:Renin-Angiotensin System / Q000187:drug effects; D012982:Sodium, Dietary / Q000494:pharmacology*
D015342:DNA Probes; D007527:Isoenzymes; D012333:RNA, Messenger; D012982:Sodium, Dietary; D000325:Adrenodoxin; D000450:Aldosterone; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; D002216:Captopril; D011188:Potassium