Effects of Chronic Clonidine Administration on Sympathetic Nerve Traffic and Baroreflex Function in Heart Failure

Turri, C; Seravalle, Gino; Bertinieri, G.; Pierini, Alberto; Mancia, Giuseppe

doi:10.1161/01.hyp.38.2.286

Cited by 29 publications

(24 citation statements)

References 39 publications

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“…The addition of moxonidine had no influence on baroreceptor sensitivity-that is, the capacity to increase or decrease MSNA or heart rate to buffer short-term BP fluctuations. In that respect, moxonidine does not differ from clonidine, which also does not affect baroreceptor sensitivity, when assessed by identical methodology (22,23).…”

Section: Discussionmentioning

confidence: 92%

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Moxonidine Normalizes Sympathetic Hyperactivity in Patients with Eprosartan-Treated Chronic Renal Failure

Neumann¹,

Ligtenberg²,

Oey³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Enalapril and losartan reduce but not normalize sympathetic hyperactivity in patients with hypertensive chronic renal failure (CRF). This study assessed the effect of chronic eprosartan on BP and sympathetic activity, and assessed the effect of moxonidine during chronic eprosartan treatment. In 11 stable patients with CRF (creatinine clearance 47 Ϯ 10 ml/min), muscle sympathetic nerve activity (MSNA; peroneal nerve), BP, and baroreceptor sensitivity were measured in the absence of antihypertensive drugs (except diuretics) during chronic eprosartan therapy (600 mg for 6 wk) and in 9 patients after moxonidine (0.2 mg for 6 wk) was added. Normovolemia was controlled by diuretics and confirmed by extracellular fluid volume measurements. BP, heart rate, and MSNA were higher in patients than in 22 controls.During eprosartan therapy, mean arterial pressure (111 Ϯ 9 to 98 Ϯ 7 mmHg, P Ͻ 0.001), heart rate (71 Ϯ 10 to 65 Ϯ 8 bpm, P Ͻ 0.001), and MSNA (35 Ϯ 10 to 27 Ϯ 8 bursts/min, P Ͻ 0.001) decreased. After the addition of moxonidine (n ϭ 9), a further reduction of mean arterial pressure to 89 Ϯ 7 mmHg (P Ͻ 0.05) and of MSNA to 20 Ϯ 10 bursts/min (P Ͻ 0.05) occurred. Sympathetic activity in patients with CRF can be normalized, and angiotensin II-independent sympathetic hyperactivity contributes to the pathogenesis of renal hypertension. Sympathetic hyperactivity is associated with poor cardiovascular outcomes, implying that reduction might be beneficial to the patients. The addition of moxonidine to angiotensin II antagonist treatment might be appropriate.Chronic renal failure (CRF) is often characterized by the presence of sympathetic hyperactivity (1-3). This contributes to the pathogenesis of renal hypertension. It is also associated with cardiovascular morbidity and mortality independently of its effect on BP (4). These data suggest that reducing sympathetic hyperactivity might be beneficial. Previously we have shown that both the angiotensin-converting enzyme (ACE) inhibitor enalapril and the angiotensin II (AngII) antagonist losartan reduce but not normalize sympathetic hyperactivity, when quantified by measuring muscle sympathetic nerve activity (MSNA) (5,6). These studies indicate that AngII mediated mechanisms are important in the pathogenesis of renal hypertension. The data also suggest that an additional intervention is needed to normalize sympathetic activity.Eprosartan is an AngII antagonist with a chemical structure distinct from losartan and most other AngII antagonists. Some but not all experimental evidence suggests that eprosartan has a higher affinity to presynaptic Ang receptors than other AngII antagonists, thereby more effectively reducing sympathetic activity (7,8). In the study presented here, we evaluated in patients with CRF the effects of eprosartan on BP and MSNA. Second, we hypothesized that if sympathetic activity is not normalized during chronic eprosartan, addition of a centrally acting sympatholytic agent with a mode of action different from AngII antagonists would further decre...

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Section: Discussionmentioning

confidence: 92%

“…This finding points to mechanism(s) independent of the renin-angiotensin system in the pathogenesis of sympathetic hyperactivity. Also, in patients with heart failure who receive chronic treatment with an ACE inhibitor or AngII antagonist, MSNA was normalized only after the addition of clonidine (22).…”

Section: Discussionmentioning

confidence: 99%

Moxonidine Normalizes Sympathetic Hyperactivity in Patients with Eprosartan-Treated Chronic Renal Failure

Neumann¹,

Ligtenberg²,

Oey³

et al. 2004

Journal of the American Society of Nephrology

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“…Similarly, sympatholytic medications acting in the brain, such as clonidine, reduce sympathetic nervous system activity and blood pressure. [25][26][27] The hypothesis that blood pressure reduction is mediated through the central nervous system is further supported by the time course of the response. Normally, blood pressure reduction elicits a baroreflex-mediated increase in heart rate and in circulating renin concentrations.…”

Section: Discussionmentioning

confidence: 98%

Carotid Baroreceptor Stimulation, Sympathetic Activity, Baroreflex Function, and Blood Pressure in Hypertensive Patients

et al. 2010

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Abstract-In animals, electric field stimulation of carotid baroreceptors elicits a depressor response through sympathetic inhibition. We tested the hypothesis that the stimulation acutely reduces sympathetic vasomotor tone and blood pressure in patients with drug treatment-resistant arterial hypertension. Furthermore, we tested whether the stimulation impairs the physiological baroreflex regulation. We studied 7 men and 5 women (ages 43 to 69 years) with treatment-resistant arterial hypertension. A bilateral electric baroreflex stimulator at the level of the carotid sinus (Rheos) was implanted Ն1 month before the study. We measured intra-arterial blood pressure, heart rate, muscle sympathetic nerve activity (microneurography), cardiac baroreflex sensitivity (cross-spectral analysis and sequence method), sympathetic baroreflex sensitivity (threshold technique), plasma renin, and norepinephrine concentrations. Measurements were performed under resting conditions, with and without electric baroreflex stimulation, for Ն6 minutes during the same experiment. Intra-arterial blood pressure was 193Ϯ9/94Ϯ5 mm Hg on medications. Acute electric baroreflex stimulation decreased systolic blood pressure by 32Ϯ10 mm Hg (range: ϩ7 to Ϫ108 mm Hg; Pϭ0.01). The depressor response was correlated with a muscle sympathetic nerve activity reduction (r 2 ϭ0.42; PϽ0.05). In responders, muscle sympathetic nerve activity decreased sharply when electric stimulation started. Then, muscle sympathetic nerve activity increased but remained below the baseline level throughout the stimulation period. Heart rate decreased 4.5Ϯ1.5 bpm with stimulation (PϽ0.05). Plasma renin concentration decreased 20Ϯ8% (PϽ0.05). Electric field stimulation of carotid sinus baroreflex afferents acutely decreased arterial blood pressure in hypertensive patients, without negative effects on physiological baroreflex regulation. The depressor response was mediated through sympathetic inhibition. (Hypertension. 2010;55:619-626.)

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“…Clonidine, an ␣ 2 and I 1 receptor agonist, has been used for this purpose. Grassi et al 12 have recently reported a 26% reduction in muscle sympathetic burst frequency and a 47% fall in PNE concentrations after 2 months of 0.1 mg clonidine daily, administered by transdermal patch. More selective I 1 agonists, such as rilmenidine and moxonidine, have fewer side effects than clonidine.…”

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confidence: 98%

The “Unsympathetic” Nervous System of Heart Failure

Floras

2002

Circulation

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Effects of Chronic Clonidine Administration on Sympathetic Nerve Traffic and Baroreflex Function in Heart Failure

Cited by 29 publications

References 39 publications

Moxonidine Normalizes Sympathetic Hyperactivity in Patients with Eprosartan-Treated Chronic Renal Failure

Moxonidine Normalizes Sympathetic Hyperactivity in Patients with Eprosartan-Treated Chronic Renal Failure

Carotid Baroreceptor Stimulation, Sympathetic Activity, Baroreflex Function, and Blood Pressure in Hypertensive Patients

The “Unsympathetic” Nervous System of Heart Failure

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