Regulation of 11 beta-hydroxylase cytochrome p450 expression by cholesterol in spontaneously hypertensive rats.
J Hypertens
; 13(11): 1253-8, 1995 Nov.
Article
en En
| MEDLINE
| ID: mdl-8984122
ABSTRACT
OBJECTIVE:
To investigate whether hypercholesterolaemia interferes with the expression of the enzymes involved in steroid biosynthesis in the adrenal cortex.METHODS:
Twenty-four 5-week-old male spontaneously hypertensive rats (SHR) were randomly assigned to a high (1%) cholesterol diet (n = 8) or to a matched cholesterol-free diet (n = 8) for 6 weeks. A third group (n = 8) was studied after 2 weeks of washout from the high-cholesterol intake. A cohort of age- and sex-matched normotensive Wistar-Kyoto (WKY) rats (n = 24) underwent the same treatments and was used as a control.RESULTS:
In SHR cholesterol feeding reduced urinary sodium excretion (0.8 +/- 0.1 versus 1.4 +/- 0.1 mmol/24 h in the cholesterol-free group), increased plasma aldosterone levels (299 +/- 60 versus 154 +/- 24) and reduced plasma corticosterone levels (142 +/- 21 versus 278 +/- 35 ng/ml). Those responses were associated with a reduction of 11 beta-hydroxylase cytochrome P450 messenger RNA (mRNA) in the adrenal cortex (-52.3 +/- 3.4%) whereas aldosterone synthase mRNA remained unchanged. That effect and the changes in electrolyte excretion and steroid levels were no longer detectable after withdrawal of the diet. In WKY rats high-cholesterol diet induced no significant changes in urinary electrolyte excretion, steroid levels and expression of 11 beta-hydroxylase cytochrome P450 and aldosterone synthase in the adrenals.CONCLUSIONS:
The present results indicate that in SHR hypercholesterolaemia selectively interferes with the adrenal steroid biosynthetic pathway by reducing the expression of 11 beta-hydroxylase, leading to accumulation of mineralocorticoids and sodium retention.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ratas Endogámicas SHR
/
Colesterol en la Dieta
/
Esteroide 11-beta-Hidroxilasa
/
Hipertensión
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Hypertens
Año:
1995
Tipo del documento:
Article
País de afiliación:
Italia