19343
document
[ Rilmenidine sympatholytic activity preserves mental and orthostatic sympathetic response and epinephrine secretion ] . BACKGROUND Heightened central sympathetic nervous outflow is common in essential hypertension , contributing to hypertension development and perhaps also to complications . Acute sympathetic nervous activation is a proven trigger for adverse cardiovascular events . Accordingly , antihypertensive drugs inhibiting sympathetic outflow represent a theoretically attractive therapeutic option . OBJECTIVES To study the sympatholytic and blood pressure lowering activity of the imidazoline binding agent rilmenidine at rest and during reflex sympathetic activation . DESIGN AND METHODS The HERA study ( Hyperium Effect on the sympathetic Reflex activation and Adrenaline ) is a randomised , double-blind , 6-week cross-over trial , with a 1-week placebo run-in period , two 2-week active treatment intervals ( rilmenidine 1 mg bid , placebo ) and intervening one week placebo wash-out . In 15 hypertensive patients , noradrenaline and adrenaline plasma kinetics and intra-arterial blood pressure measurements were performed at rest , after mental stress ( difficult mental arithmetic ) and during head-up tilting , at the end of the 2-week dosing periods . RESULTS The noradrenaline spillover rate , indicative of whole body sympathetic activity , was reduced 35 % by rilmenidine at rest ( p < 0.01 ) and remained significantly lower during mental stress and tilting , although the increases in noradrenaline spillover with both stimuli were preserved . The effects on intraarterial blood pressure ran in parallel , a fall in supine resting pressure , but no reduction in BP rise during mental stress and a lack of fall in BP with tilting . On placebo , adrenaline secretion was 162 +/- 27 ng/min ( mean , SE ) at rest , increased by 77 +/- 42 ng/min with mental stress ( p=0.019 ) and was unchanged with tilting . Rilmenidine left adrenaline secretion untouched under all conditions . CONCLUSIONS This study confirms a sympatholytic effect of rilmenidine during supine rest but demonstrates that sympathetic responses during mental stress and tilting are preserved , the latter underlying a perhaps surprising absence of postural hypotension on the drug . The absence of suppression of reflexive sympathetic responses contrasts with the effects of rilmenidine in experimental animals , and emphasises the previously demonstrated unique importance in humans of suprabulbar noradrenergic neuronal projections from the brainstem , which are inhibited by imidazoline binding agents , in regulating tonic sympathetic activity in essential hypertension . Sympathetic nervous inhibition with rilmenidine contrasted with an absence of suppression of the secretion of adrenaline affirming that here , as elsewhere , sympathetic nervous and adrenal medullary function can be disconnected .
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Intervention_Pharmacological
Rilmenidine
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Intervention_Pharmacological
rilmenidine
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Intervention_Control
placebo
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Intervention_Pharmacological
rilmenidine
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Intervention_Control
placebo
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Intervention_Control
placebo
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Outcome_Mental
mental and orthostatic sympathetic response
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Outcome_Physical
epinephrine secretion ]
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Outcome_Adverse-effects
adverse cardiovascular events
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Outcome_Physical
sympatholytic and blood pressure lowering activity
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Outcome_Physical
noradrenaline and adrenaline plasma kinetics and intra-arterial blood pressure measurements
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Outcome_Physical
noradrenaline spillover
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Outcome_Physical
intraarterial blood pressure
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Outcome_Physical
BP rise
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Outcome_Physical
BP
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Outcome_Physical
adrenaline secretion
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Outcome_Physical
adrenaline secretion
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Outcome_Physical
sympathetic responses
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Outcome_Physical
tonic sympathetic activity
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Outcome_Mental
sympathetic nervous
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Outcome_Physical
and adrenal medullary function
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Participant_Sample-size
15
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Participant_Condition
hypertensive patients