Intravenous alprazolam challenge in normal subjects
A simultaneous analysis of the interrelationships between mean blood pressure (MBP), plasma catecholamines, plasma renin activity (PRA) and aldosterone, exchangeable body sodium, and blood volume was carried out before and after acute and chronic administration of clonidine in 15 patients with essential hypertension, in order to further elucidate the mechanism(s) of action of this drug. After a single oral dose of 200 microgram, clonidine produced a significant fall in MBP, heart rate, plasma norepinephrine (NE), PRA, and aldosterone. There were significant correlations (P < 0.01) between NE and MBP, but not between PRA or aldosterone and MBP both before and after the ingestion of clonidine. Furthermore, there was a significant correlation (P < 0.05) between the magnitude of fall of plasma NE and change in MBP. After 6 weeks of treatment, conidine at a dose of 960 +/- 80 microgram/day produced a significant decrement in MBP and NE, but not in PRA and aldosterone; with upright posture, the magnitude of the fall in MBP was significantly greater (P < 0.01), and the rise in plasma NE was significantly smaller (P < 0.01) after chronic clonidine treatment. There was also a significant fall (P < 0.01) in exchangeable sodium and plasma volume. The data provide evidence that inhibition of the sympathetic nervous system by clonidine plays a major role and that the decrease in exchangeable body sodium and blood volume after chronic treatment may contribute to the antihypertensive action of the drug.