摘要
Background: heightened central sympathetic nervous outflow is common in essent ial hypertension, contributing to hypertension development and perhaps also to c omplications. Acute sympathetic nervous activation is a proven trigger for adver se cardiovascular events. Accordingly, antihypertensive drugs inhibiting sympath etic outflow represent a theoretically attractive therapeutic option. Objectives : To study the sympatholytic and blood pressure lowering activity of the imidazo line binding agent rilmenidine at rest and during reflex sympathetic activation. Design and methods: the HERA study (Hyperium Effect on the sympathetic Reflex a ctivation and Adrenaline) is a randomised, double blind, 6-week cross over tr ial, with a 1-week placebo run in period, two 2-week active treatment interva ls (rilmenidine 1 mg bid, placebo) and intervening one week placebo wash out. I n 15 hypertensive patients, noradrenaline and adrenaline plasma kinetics and int ra arterial blood pressure measurements were performed at rest, after mental st ress (difficult mental arithmetic) and during head up tilting, at the end of th e 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 e ffects 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 i n 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 uncha nged with tilting. Rilmenidine left adrenaline secretion untouched under all con ditions. Conclusions: this study confirms a sympatholytic effect of rilmenidine during supine rest but demonstrates that sympathetic responses duringmental stre ss and tilting are preserved, the latter underlying a perhaps surprising absence of postural hypotension on the drug. The absence of suppression of reflexive sy mpathetic responses contrasts with the effects of rilmenidine in experimental an imals, and emphasises the previously demonstrated unique importance in humans of suprabulbar noradrenergic neuronal projections from the brainstem, which are in hibited by imidazoline binding agents, in regulating tonic sympathetic activity in essential hypertension. Sympathetic nervous inhibition with rilmenidine contr asted with an absence of suppression of the secretion of adrenaline affirming th at here, as elsewhere, sympathetic nervous and adrenal medullary function can be disconnected.
Background: heightened central sympathetic nervous outflow is common in essent ial hypertension, contributing to hypertension development and perhaps also to c omplications. Acute sympathetic nervous activation is a proven trigger for adver se cardiovascular events. Accordingly, antihypertensive drugs inhibiting sympath etic outflow represent a theoretically attractive therapeutic option. Objectives : To study the sympatholytic and blood pressure lowering activity of the imidazo line binding agent rilmenidine at rest and during reflex sympathetic activation. Design and methods: the HERA study (Hyperium Effect on the sympathetic Reflex a ctivation and Adrenaline) is a randomised, double blind, 6-week cross over tr ial, with a 1-week placebo run in period, two 2-week active treatment interva ls (rilmenidine 1 mg bid, placebo) and intervening one week placebo wash out. I n 15 hypertensive patients, noradrenaline and adrenaline plasma kinetics and int ra arterial blood pressure measurements were performed at rest, after mental st ress (difficult mental arithmetic) and during head up tilting, at the end of th e 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 e ffects 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 i n 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 uncha nged with tilting. Rilmenidine left adrenaline secretion untouched under all con ditions. Conclusions: this study confirms a sympatholytic effect of rilmenidine during supine rest but demonstrates that sympathetic responses duringmental stre ss and tilting are preserved, the latter underlying a perhaps surprising absence of postural hypotension on the drug. The absence of suppression of reflexive sy mpathetic responses contrasts with the effects of rilmenidine in experimental an imals, and emphasises the previously demonstrated unique importance in humans of suprabulbar noradrenergic neuronal projections from the brainstem, which are in hibited by imidazoline binding agents, in regulating tonic sympathetic activity in essential hypertension. Sympathetic nervous inhibition with rilmenidine contr asted with an absence of suppression of the secretion of adrenaline affirming th at here, as elsewhere, sympathetic nervous and adrenal medullary function can be disconnected.
