Effect of centrally acting alpha-adrenergic agonists on sympathetic nervous system function in humans

Morris J. Brown, Deborah Harland, Micheal B. Murphy, Alan D. Struthers

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    8 Citations (Scopus)

    Abstract

    Three studies were undertaken to reevaluate whether there is a peripheral component in the reduction of sympathetic activity caused by centrally acting drugs; and whether the antihypertensive effect of these drugs is due entirely to this reduction. Plasma growth hormone and norepinephrine concentrations were used as respective markers of central alpha-adrenoceptor stimulation and peripheral sympathetic activity. In six normal volunteers, intravenous infusion of 0.2 mg clonidine and 2 mg guanfacine was compared. The falls in systolic blood pressure and plasma norepinephrine concentration were slightly greater after clonidine (18 mm Hg and 0.22 ng/ml) than after guanfacine (12 mm Hg and 0.13 ng/ml) administration. These falls occurred earlier than the rise in growth hormone, which rose to a maximum of 23 and 20 IU/ml respectively at 45 minutes after dosing. In six patients with essential hypertension clonidine and alpha-methyldopa caused similar falls in blood pressure and plasma norepinephrine concentration although these changes occurred later with alpha-methyldopa. Plasma growth hormone levels remained undetectable in most patients. In Wistar rats the effect of central and peripheral alpha 2-blockade on clonidine-induced changes was compared. Two groups of six rats received intravenous RX 781094, 0.3 mg/kg, or vehicle 10 minutes before receiving clonidine, 5 micrograms/kg i.v. In the latter, control group, clonidine reduced mean blood pressure by 30.7 +/- 1.9 mm Hg and heart rate by 46 +/- 6.7 beats/min. Plasma norepinephrine fell from 0.22 +/- 0.023 ng/ml to 0.116 +/- 0.013 ng/ml. After pretreatment with RX 781094, blood pressure did not change and heart rate fell by 18 +/- 2.7 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)
    Original languageEnglish
    Pages (from-to)II57-II62
    Number of pages6
    JournalHypertension
    Volume6
    Issue number5 pt. 2
    DOIs
    Publication statusPublished - 1984

    Keywords

    • Clonidine
    • Alpha-methyldopa
    • Guanfacine
    • RX 781094 (idazoxan)
    • Blood pressure
    • Plasma norepinephrine

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