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Tissue Distribution and Hypotensive Effect of Prazosin in the Conscious Rat

We investigated the hypotensive effect and tissue distribution of prazosin (1 mg/kg i.v.) in conscious rats. This dose caused an immediate fall in blood pressure, associated with a nonsignificant increase in heart rate. Blood pressure then gradually rose to control over a 2-h period. Prazosin was measured in plasma and tissue samples by high-pressure liquid chromatography. Highest concentrations of drug were found in liver and kidney and the lowest in brain. The rate of decline of prazosin from plasma was similar to its decline from the tissues, indicating a rapid equilibrium. This rate of disappearance was also similar to the decay of the hypotensive response and suggests that prazosin in plasma may be in equilibrium with prazosin at its site of action.