Journal of hypertension · 1995
Regulation of 11 beta-hydroxylase cytochrome p450 expression by cholesterol in spontaneously hypertensive rats.
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Rubattu S, Russo R, Gigante B, Porcellini A, Finizia L, Trimarco B, Volpe M
Аннотация
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.
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.