Both low sodium and high potassium intake increase the level of adrenal angiotensin-II receptor type 1, but not that of adrenocorticotropin receptor.
Angiotensin-II (AII), a component of the renin-angiotensin system, is the major factor that regulates the formation of aldosterone in the adrenal cortex zona glomerulosa (ZG). The activity of this system is increased by an increase in potassium intake or a decrease in sodium intake. Using immunoblotting analysis, we determined whether these ions affect the expression of type 1 AII receptors (AT1) and compared the results thus obtained with the AT1 receptor mRNA levels. We also studied the interrelation among AII, AT1 receptors, cytochrome P450 aldosterone synthase (P450c18), and plasma aldosterone levels in rats fed a normal diet or a low sodium or high potassium diet with or without captopril, an inhibitor of angiotensin-converting enzyme, for 7 days. The effects of ions on the level of ACTH receptor mRNA were also analyzed. We found that a low sodium intake increased plasma aldosterone levels from 5.5 to 236 ng/dl and led to 2.3- and 3.7-fold increases in the levels of adrenal ZG AT1 receptor protein and AT1 receptor mRNA, whereas a 11.8-fold increase was found in the level of P450c18 mRNA. Captopril almost completely reversed these effects. We have shown that a high potassium intake increased plasma aldosterone levels to 25.9 ng/dl and also led to 1.84- and 1.95-fold increases in the level of ZG AT1 receptor protein and AT1 receptor mRNA, whereas the ZG P450c18 mRNA level was increased 3.5-fold. The plasma aldosterone level of animals fed a high diet of potassium and captopril was still higher than that in control animals at 16.6 ng/dl, and the levels of ZG AT1 receptor and P450c18 mRNAs were only slightly less than those of the high potassium groups, indicating that captopril did not efficiently block aldosterone formation under these conditions. ACTH receptor mRNA levels remain unaffected by either low sodium or high potassium intake. Collectively, these results indicate that the increased aldosterone secretion induced by low sodium or high potassium intake involves concomitant increases in AT1 receptor and P450c18 mRNAs, which are effectively translated into their respective proteins, and that the expression of both proteins is mediated in part by AII.
Lehoux
J G
JG
Department of Biochemistry, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
Bird
I M
IM
Rainey
W E
WE
Tremblay
A
A
Ducharme
L
L
D000450:Aldosterone / Q000097:blood / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002216:Captopril / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004032:Diet; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology*; D012313:RNA / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D018043:Receptors, Corticotropin / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D012982:Sodium, Dietary / Q000494:pharmacology*; D013252:Steroid 11-beta-Hydroxylase / Q000096:biosynthesis; D015383:Zona Fasciculata / Q000187:drug effects / Q000378:metabolism; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*; D015385:Zona Reticularis / Q000187:drug effects / Q000378:metabolism
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D018043:Receptors, Corticotropin; D012982:Sodium, Dietary; D000804:Angiotensin II; D000450:Aldosterone; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; D002216:Captopril; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D011188:Potassium