Mechanism of Elevated Plasma Noradrenaline in the Course of Essential Hypertension

Esler, Murray; Jennings, Garry; Biviano, Brendan; Lambert, Gavin W.; Hasking, Gregory J.

doi:10.1097/00005344-198608005-00008

Cited by 122 publications

(68 citation statements)

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“…11,[22][23][24] Previously, convincing data suggested the involvement of enhanced sympathetic activity in the pathogenesis of cardiovascular diseases, including hypertension and hypertension-related complications. [25][26][27] Sympathetic overactivity might be partly explained by peripheral mechanisms, including elevated peripheral chemoreceptor activity, reduced baroreceptor sensitivity and reduced nitric oxide synthesis. [28][29][30][31][32] Statins can affect baroreceptor sensitivity, 33 endothelial function 17 and nitric oxide synthesis; 18 thus, the speculation arose that statins might modulate sympathetic outflow in cardiovascular disorders.…”

Section: Discussionmentioning

confidence: 99%

Simvastatin reduces sympathetic activity in men with hypertension and hypercholesterolemia

et al. 2010

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Beyond their hypolipidemic effect, statins reduce cardiovascular risk in hypertensive subjects via various mechanisms; one suggested mechanism is that they reduce sympathetic activity. We investigated the hypothesis that simvastatin decreased muscle sympathetic nerve activity (MSNA) in 31 hypertensive subjects with hypercholesterolemia (aged 38.7±10 years). In this randomized, placebocontrolled, double-blinded study, patients were treated with simvastatin (40 mg day À1 ; n¼15) or placebo (n¼16) for 8 weeks. Before and after treatment, we measured MSNA, blood pressure and heart rate. Baroreceptor control of the heart rate, or baroreceptor sensitivity (BRS), was computed by the sequence method, a cross-analysis of systolic blood pressure and the electrocardiogram R-R interval. Blood samples were tested for plasma levels of catecholamines, neuropeptide Y, aldosterone, endothelin and renin activity. Simvastatin significantly reduced MSNA (from 36.5 ± 5 to 27.8 ± 6 bursts per min, P¼0.001), heart rate (from 77 ± 6.7 to 71 ± 6.1 beats per min, P¼0.01) and both total and low-density lipoprotein cholesterol (from 249±30.6 to 184±28.3 mg dl À1 , P¼0.001 and from 169±30.6 to 117±31.2 mg dl À1 , P¼0.01, respectively). Simvastatin also improved BRS (from 10.3 ± 4.1 to 17.1 ± 4.3 ms per mm Hg, P¼0.04). No changes were observed in systolic or diastolic blood pressures, or in plasma levels of catecholamines, neuropeptide Y, endothelin, aldosterone and renin activity. After simvastatin therapy, MSNA and BRS were inversely related (r¼À0.94, Po0.05). In conclusion, we found that, in patients with hypertension and hypercholesterolemia, simvastatin reduced MSNA, and this was related to increased baroreceptor sensitivity.

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Section: Discussionmentioning

confidence: 99%

Simvastatin reduces sympathetic activity in men with hypertension and hypercholesterolemia

et al. 2010

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“…In healthy subjects measurements of noradrenaline spillover support the notion that the sympathetic firing is higher in elderly than in younger patients. 10,11,14 In hypertensive patients, however, an opposite behaviour has been demonstrated. 10 Moreover, the increased concentration of the neurotransmitter does not necessarily translate into an enhanced cardiac responsiveness, which was found to be decreased on the basis of the reduced HRV.…”

Section: Allmentioning

confidence: 99%

“…8,9 Whether the activity of the autonomic nervous system to the heart is influenced by aging in hypertensive patients remains uncertain, owing to discrepancies in the results of different methods currently used to evaluate the sympathetic control of the cardiovascular system in these patients. In fact, in spite of an increased noradrenaline spillover, 10,11 total heart rate variability (HRV) and the variability of low-frequency oscillations were markedly reduced in elderly healthy subjects, 12,13 suggesting that endorgan responsiveness may be impaired with age, 14 because of alterations of the ␤-adrenergic receptor and/or its postreceptor signal transduction pathway.…”

Section: Introductionmentioning

confidence: 99%

Cardiac autonomic modulation and incidence of late potentials in essential hypertension: role of age, sex, ventricular mass and remodeling

et al. 1998

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“…9 Renal NE spillover in hypertensive patients is also a function of age. 27 Compared to age-matched normotensive controls, hypertensive patients \40 years old have been shown to have a significantly higher rate of renal NE spillover, and this difference diminished with increasing age. 10 Similar findings have been reported in animal studies, suggesting that the renal sympathetic nerves may have a greater effect on the development (younger patients) than on the maintenance (older patients) of hypertension.…”

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confidence: 99%

“…In contrast, renal NE spillover is selective for the kidney, and elevations in renal NE spillover in hypertensive patients, 27 as well as reductions in renal NE spillover after renal artery denervation, have been demonstrated. 7,28 Future studies designed to determine whether there is a relationship between renal 123 I-mIBG scintigraphy and renal NE spillover, rather than MSNA, would provide a more direct evaluation of renal sympathetic nerve function in patients with uncontrolled hypertension.…”

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confidence: 99%

123I-mIBG scintigraphy: Clinical tool for assessing renal sympathetic activity?

George

Bhambhvani

Oparil

2017

Journal of Nuclear Cardiology

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See related article, pp. 363-371Among patients with treatment-resistant hypertension, transcatheter renal denervation has been shown to reduce blood pressure (BP) in a number of uncontrolled, unblinded clinical trials.1 However, in a prospective, single-blind, randomized trial that compared transcatheter renal denervation to a sham procedure, there was no significant difference in systolic BP between the two treatment arms at 6 months follow-up.2 Proposed reasons for the lack of benefit include a substantial placebo effect related to the procedure, differences in medication adherence such that the sham-treated control group may have taken more antihypertensive medications, operator inexperience with transcatheter renal denervation, and performance of an inadequate number of ablations in each renal artery.3 It has been postulated that operator inexperience and performance of too few ablations may have led to incomplete denervation and therefore an inadequate BP response to the procedure. The absence of a readily available methodology to define completeness of transcatheter renal denervation in humans remains as an unmet need in defining the potential role of the procedure in clinical practice.The contribution of increased renal sympathetic tone to the pathophysiology of hypertension has been known for decades. Surgical renal denervation in hypertensive animal models has been shown to cause significant decreases in BP compared to sham controls. 4 A commonly employed method of surgical denervation involves stripping the adventitia from the renal artery of hypertensive rats and exposing the artery to phenol, a compound that irreversibly blocks neural conduction. 5Renal norepinephrine (NE) content measured at specified time points after surgical denervation in hypertensive rats has been shown to decrease dramatically (94% reduction compared to sham-controlled rats at 1 week; P \ 0.001), suggesting complete ablation of the renal nerves. A positive correlation was also shown between absolute change in BP after denervation and renal NE content in denervated animals (r = 0.80, P \ 0.001). 4In the clinical research setting, a number of methods have been utilized to assess the completeness of renal denervation in hypertensive humans. The most promising and best characterized are the measurements of muscle sympathetic nerve activity (MSNA), renal NE spillover rate, and assessment of sympathetically mediated responses to electrical stimulation of the renal artery before and after denervation.6-8 Assessment of MSNA is minimally invasive and entails percutaneous insertion of a recording electrode into a superficial nerve (peroneal or radial), allowing direct recording of postganglionic sympathetic neural bursts. MSNA reflects moment-to-moment sympathetic outflow from the central nervous system to either skeletal muscle or skin, but does not provide direct information on sympathetic outflow to the kidney or heart. 9Renal NE spillover is assessed by infusing small doses of radiolabeled NE intravenously and measuring its level in...

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Mechanism of Elevated Plasma Noradrenaline in the Course of Essential Hypertension

Cited by 122 publications

References 0 publications

Simvastatin reduces sympathetic activity in men with hypertension and hypercholesterolemia

Simvastatin reduces sympathetic activity in men with hypertension and hypercholesterolemia

Cardiac autonomic modulation and incidence of late potentials in essential hypertension: role of age, sex, ventricular mass and remodeling

123I-mIBG scintigraphy: Clinical tool for assessing renal sympathetic activity?

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