Different regulation of cardiac and renal corticosteroid receptors in aldosterone-salt treated rats: effect of hypertension and glucocorticoids.
This study analysed the regulation of cardiac mineraloreceptor (MR) and glucoreceptor (GR) in aldosterone-salt treatment (AST). AST causes hypertension, left ventricle (LV) hypertrophy and decreases plasma corticosterone level. Ribonuclease protection assay and Western blot analysis showed a rise of MR mRNA (1.5- and 1.4-fold at day 15 and 30, respectively) and protein levels (1.8- and 4.1-fold at day 30 and 60, respectively) in the LV, but not in either the right ventricle (RV) or in kidney of treated rats. Addition of MR antagonist spironolactone (20 mg/kg/day) for 30 days failed to prevent these changes but was able to reduce AST-induced cardiac fibrosis. Similar hypertension-induced MR upregulations were observed in the LV of AngII-hypertensive rats and of 12-week-old SHR when compared to 4-week-old prehypertensive SHR. AST also enhanced left ventricular GR mRNA (2.0- and 3.0-fold at day 7 and 15, respectively) and protein contents (2.0- and 1.7-fold at day 30 and 60, respectively). In contrast to MR, GR levels were also upregulated in both RV and kidney. Such an upregulation was equally observed at mRNA and protein levels in LV, RV and kidney after adrenalectomy (15 days) and was prevented in both tissues after glucocorticoid replacement (adrenalectomy + dexamethasone at 100 micro g/kg/day for 15 days). Therefore, MR level may be controlled by hemodynamical factors whereas that of GR depends upon glucocorticoids level.
Silvestre
J S
JS
INSERM U127, Hôpital Lariboisière, IFR circulation, Université Paris 7-Denis Diderot, Paris cedex 10, 75475, France.
Robert
V
V
Escoubet
B
B
Heymes
C
C
Oubénaïssa
A
A
Desopper
C
C
Swynghedauw
B
B
Delcayre
C
C
D000315:Adrenalectomy; D000367:Age Factors; D000450:Aldosterone / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D015153:Blotting, Western; D003094:Collagen / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D018075:RNA, Complementary / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D011987:Receptors, Steroid / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology*; D013148:Spironolactone / Q000494:pharmacology; D013997:Time Factors
D005938:Glucocorticoids; D000451:Mineralocorticoid Receptor Antagonists; D018075:RNA, Complementary; D011987:Receptors, Steroid; D000804:Angiotensin II; D013148:Spironolactone; D012965:Sodium Chloride; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D003094:Collagen