Physiologic mechanisms opposing the hemodynamic effects of prazosin

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Abstract
Prazosin was given for 10-14 days to 8 hypertensive patients on a fixed intake of dietary salt. Except as limited by side effects, the dose was increased from 2 mg/day to a maximum dose of 24 mg/day. During treatment, when subjects were studied in supine and upright positions, mean arterial pressure (MAP) fell 6% and 12% (P < 0.025 and P < 0.005), heart rate rose 3% and 9% (P < 0.05 and P < 0.005) and plasma norepinephrine increased 95% and 107% (P < 0.01 and P < 0.001) over control. Daily excretion of the norepinephrine metabolites methoxyhydroxyphenyl glycol and vanillylmandelic acid increased 42% and 17% (P < 0.05 for each) during treatment. There were no changes in average body weight or plasma renin for the group, but patients whose body weight increased tended to show less reduction in blood pressure (r = 0.72, P < 0.05) and smaller increases in heart rate (r = -0.73, P < 0.05) during treatment with prazosin. Expansion of extracellular fluid and activation of the sympathetic nervous system apparently oppose the hemodynamic effects of prazosin.