Androgens increase blood pressure in orchiectomized male Wistar rats similar to high salt diet

Peter Hofmann1, Marten Michaelis1, Franziska Goetz2 & Marcus Quinkler1

1Clinical Endocrinology, Charite Campus Mitte, Berlin, Germany; 2Institute of Experimental Endocrinology, Charite, Berlin, Germany.

Introduction: With the onset of puberty blood pressure increases more in men than in women while boys and girls do not show any gender differences in blood pressure. Androgens are known to play an important role in renal tubular epithelial cell growth, hypertrophy and erythropoetin production and may be important determinants of sex-specific differences in blood pressure. However the exact mechanisms are not clear yet.

Methods: Male Wistar rats aged 810 weeks were orchiectomized and put on a low- (chow 0.03% NaCl+tap water) or high-salt diet (chow 4% NaCl+trinking water 0.09% NaCl) over 5 weeks. In addition they received either placebo, testosterone (1 mg/animal) or 5alpha-dihydrotestosterone (1 mg/animal) as daily s.c. injection over 16 days (each group n=6). In further experiments rats were treated with mineralocorticoid antagonist spironolactone (50 mg/kg weight per day) or androgen receptor antagonist flutamide (30 mg/kg weight per day) additionally to testosterone or 5alpha-dihydrotestosterone. Blood pressure was measured non-invasively using the tail-cuff method. 24 h urine samples were collected in metabolic cages and blood and organs were secured after decapitation.

Results: Blood pressure significantly increased and aldosterone serum concentrations decreased due to high salt diet. This effect could be abolished by spironolactone as well as by flutamide. Testosterone and 5alpha-dihydrotestosterone significantly increased blood pressure in rats on a low salt diet. This effect could be diminished by flutamide and by spironolactone. The highly elevated aldosterone levels in rats on low salt diet with spironolactone or flutamide treatment were reduced by androgen treatment.

Conclusions: These results highlight the possible interaction of androgens with the mineralocorticoid pathway, probably via an androgen effect on the renal epithelial sodium channel (ENaC). Our data might give new insight into mechanisms responsible for the reported gender differences in blood pressure.