Inhibition of tyrosine hydroxylase reduces dexamethasone‐induced hypertension

Chronic treatment with glucocorticoids induces hypertension. Dexamethasone (DEX), a synthetic glucocorticoid, increases the expression and activity of tyrosine hydroxylase (TH), the rate limiting step in catecholamine synthesis. We tested the hypothesis that prevention of catecholamine synthesis with the TH inhibitor, α‐methyl‐para‐tyrosine (α‐MPT), decreases the pressor effect of DEX. Male Fischer 344 rats were implanted with radiotelemetry to measure mean arterial pressure (MAP) and heart rate (HR). After baseline recording, rats were injected for 3 days with either vehicle or α‐MPT (50 mg/Kg, i.p.). Rats were then treated with DEX (0.1 mg/day) in drinking water for 7 days. The administration of α‐MPT did not alter diurnal baseline MAP nor HR. Chronic treatment with DEX increased MAP by 16.2±2.1 mmHg and 17.3±2.0 mmHg, during the light and dark phases of a 24 hour period, respectively. However, MAP was reduced in the group treated with α‐MPT plus DEX by 7.7±0.4 mmHg in the light phase and 9.1±0.7 mmHg in the dark phase. Thus, inhibition of tyrosine hydroxylase activity with α‐MPT reduced DEX‐induced hypertension. These results indicate that the pressor effect of DEX depends at least in part on catecholamine synthesis by the peripheral sympathetic nervous system. Support: Department of Veterans Affairs.