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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Treatment with tetrahydrobiopterin reduces blood pressure in male SHR by reducing testosterone synthesis

Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi

Submitted 26 July 2004 ; accepted in final form 10 December 2004

Treatment with tetrahydrobiopterin (BH₄) reduces blood pressure in spontaneously hypertensive rats (SHR). In the present study, we tested the hypothesis that chronic BH₄ reduces blood pressure in male SHR by reducing testosterone biosynthesis mediated by increasing nitric oxide (NO). Male SHR, aged 17–18 wk, intact or castrated, were treated for 1 wk with BH₄ (20 mg·kg^–1·day^–1 ip). After 1 wk, mean arterial pressure (MAP), serum testosterone, and nitrate/nitrite excretion (NO_x) were measured. MAP was significantly higher in intact males than castrated males (179 ± 2 vs. 155 ± 4 mmHg, P < 0.001). In intact males, BH₄ caused a 17% reduction in MAP (148 ± 2 mmHg), had no effect on NO_x, and reduced serum testosterone by 85% (24.09 ± 2.37 vs. 3.72 ± 0.73 ng/dl; P < 0.001). In castrated males, BH₄ had no effect on MAP (152 ± 5 mmHg) but increased NO_x by 38%. When castrated males were supplemented with testosterone, MAP increased to the same level as in intact males (180 ± 7 mmHg), and BH₄ had no effect on MAP (182 ± 7 mmHg) or NO_x. NO has been shown to decrease testosterone biosynthesis. Chronic sodium nitrite (70 mg·kg^–1·day^–1 x 1 wk) decreased MAP in intact males (150 ± 4 mmHg) but had no effect on serum testosterone (21.46 ± 3.08 ng/dl). The data suggest that BH₄ reduces testosterone synthesis and thereby reduces MAP in male SHR, an androgen-dependent model of hypertension. The mechanism(s) by which BH₄ reduces serum testosterone levels are not clear, but the data do not support a role for NO as a mediator.

hypertension; castration; androgens; nitric oxide; oxidative stress

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