Role of the Sympathetic Nervous System in Blood Pressure Maintenance in Obesity

Sowers, James R.; Whitfield, L.; Catania, Robert A.; Stern, Naftali; Tuck, Michael L.; Dornfeld, Leslie; Maxwell, Morton H.

doi:10.1210/jcem-54-6-1181

Cited by 152 publications

(58 citation statements)

References 24 publications

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“…Studies examining weight loss associated with very low calorie intake (320 Kcal/day) have found that the fall in blood pressure was highly correlated with reductions in plasma NE [35,36]. They found that reduction in plasma NE and blood pressure occurred as early as 2-4 weeks after the onset of dieting.…”

Section: Discussionmentioning

confidence: 99%

A Case of Sleep Apnea Syndrome Manifesting Severe Hypertension with High Plasma Norepinephrine Levels

Makino¹,

Iwata²,

Fujiwara³

et al. 2006

Endocr J

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Abstract.A 55-year-old female was admitted to our hospital with severe hypertension (274/140 mmHg). Endocrinological examination revealed that her plasma levels of norepinephrine (NE) was elevated with high levels of urinary NE, normetanephrine and vanillylmandelic acid (VMA), suggesting the presence of pheochromocytoma. However, neither computed tomography nor MIBG scintigraphy detected any catecholamine-producing tumor in or outside the adrenal glands. She was screened with full polysomnography because of heavy snoring, and the diagnosis of severe obstructive sleep apnea syndrome (OSAS) was made. She was treated with calcium channel blocker for three weeks, but severe hypertension persisted. After treatment with nasal continuous positive airway pressure (CPAP) was added, her blood pressure gradually lowered week by week. Concomitantly, the levels of plasma and urinary NE, urinary normetanephrine and urinary VMA were normalized following nasal CPAP therapy for 2 weeks. Additional treatments with alphaadrenergic blocker further decreased her home blood pressure. After a year, she continued nasal CPAP therapy and her blood pressure was nearly below 160/100 mmHg. Urinary NE level was slightly above normal range and other catecholamines stayed within the normal range. This case shows that patients with OSAS could develop severe hypertension through elevated sympathetic tone, mimicking pheochromocytoma. Nasal CPAP therapy is recommended not only to improve hypertension and catecholamine excess but also to distinguish the condition from pheochromocytoma. THERE is a growing body of evidence showing that patients with obstructive sleep apnea syndrome (OSAS) have a high prevalence of hypertension [1][2][3] and that treatment with nasal positive airway pressure (CPAP) successfully lower blood pressure [4][5][6][7]. A major cause of hypertension in OSAS is thought to be the increased sympathetic activity due to apnea-related episodic hypoxemia and repeated arousal [8,9]. There are a number of studies demonstrating the elevated plasma or urinary norepinephrine (NE) or epinephrine (E) levels during sleep and wakefulness in OSAS [10][11][12]. Although it has been reported that nasal CPAP therapy reduces sympathetic activity [10,[13][14][15], the detailed analysis of catecholamine metabolites and the detailed time course of biochemical normalization during nasal CPAP therapy have not been fully examined. Recently, Hoy et al. reported 5 cases of OSAS with drug-resistant hypertension [16]. Catecholaminesecreting tumor could not be identified in any of these subjects, despite high urinary NE levels. Furthermore, treatment of OSAS with nasal CPAP led to normalization of both systemic blood pressure and urinary NE levels. The authors have proposed that pseudopheochromocytoma is a rare, but treatable, presentation of OSAS. Here, we present a similar rare case of the severe hypertensive OSAS patient showing high plasma and urinary catecholamine levels without evidence of catecholamine-secreting tumor. We examined the detailed profil...

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Section: Discussionmentioning

confidence: 99%

A Case of Sleep Apnea Syndrome Manifesting Severe Hypertension with High Plasma Norepinephrine Levels

Makino¹,

Iwata²,

Fujiwara³

et al. 2006

Endocr J

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“…33 The salt-sensitive hypertension that characterizes this population is associated with substantial renal injury, characterized by arteriolosclerosis, glomerulosclerosis, tubulointerstitial fibrosis, and a reduction in the GFR, 34 findings similar to those observed in our experimental study. Another example is obesity-associated hypertension, which is associated with SNS activation, 35 salt-sensitive hypertension, and renal damage with glomerulosclerosis and tubulointerstitial fibrosis. 36 Similarly, one might speculate that the routine but sometimes marked fluctuations in BP that occur daily in "normotensive" patients 37 and that are known to be triggered by the SNS 38 may be relevant to the age-related development of glomerulosclerosis and tubulointerstitial fibrosis, 39 the age-related decline in GFR, and the development of saltsensitive hypertension in this population.…”

Section: Discussionmentioning

confidence: 99%

“…15 In Situ Hybridization for Transforming Growth Factor ␤ Mouse transforming growth factor (TGF) ␤ 1 cDNA corresponding to 974 bp (421 to 1395) (gift of H.L. Moses, Vanderbilt University, Nashville, Tenn) was transcribed into 35 S-labeled antisense and sense cRNA probes. In situ hybridization was then performed on formalinfixed tissue as described.…”

Section: Immunohistological Studiesmentioning

confidence: 99%

Renal Injury and Salt-Sensitive Hypertension After Exposure to Catecholamines

et al. 1999

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Abstract-We investigated whether chronic infusion of phenylephrine could induce structural and functional changes in the kidney of rats with the subsequent development of salt-sensitive hypertension. Rats were infused with phenylephrine (0.15 mmol/kg per day) by minipump, resulting in a moderate increase in systolic blood pressure (BP) (17 to 25 mm Hg) and a marked increase in BP variability as measured by an internal telemetry device. After 8 weeks, the phenylephrine infusion was stopped with the return of BP to normal, and a nephrectomy was performed for histological studies. Glomeruli were largely spared, but focal tubulointerstitial fibrosis was present, with the de novo expression of osteopontin by injured tubules, macrophage and "myofibroblast" accumulation, and focal increases in mRNA for transforming growth factor ␤ by in situ hybridization. Peritubular capillaries at sites of injury had distorted morphology with shrinkage, rounding, and focal rarefaction, and endothelial cell proliferation was also identified. Rats were randomized to a high (8% NaCl or 1.36 mol/kg) or low (0.1% NaCl or 17 mmol/kg) salt diet. After 4 to 8 weeks, phenylephrine-treated rats on a high salt diet developed marked hypertension, which was in contrast with phenylephrine-treated rats placed on a low salt diet or vehicle-treated rats given a high salt diet. Hypertension after phenylephrine exposure correlated with the initial mean systolic BP (r 2 ϭ0.99) and the degree of BP lability (r 2 ϭ0.99) during the phenylephrine infusion, the amount of osteopontin expressed in the initial biopsy/nephrectomy (r 2 ϭ0.74), and the final glomerular filtration rate (r 2 ϭ0.58). These studies provide a mechanism by which a markedly elevated sympathetic nervous system can induce salt-dependent hypertension even when the hyperactive sympathetic state is no longer engaged. (Hypertension. 1999;34:151-159.) Key Words: phenylephrine Ⅲ renal circulation Ⅲ hypertension, episodic Ⅲ sympathetic nervous system T here is ample evidence that a hyperactive sympathetic nervous system (SNS) is present in some forms of human hypertension, especially in early, borderline essential hypertension. 1 In addition to the acute effects of SNS activation to raise blood pressure (BP), adrenergic stimulation may induce target organ damage by both hemodynamic and nonhemodynamic mechanisms. 2 Adrenergic stimulation can be associated with left ventricular hypertrophy as well as hypertrophy and stiffening of large arteries. Adrenergic agents have also been shown to stimulate vascular smooth muscle cell proliferation and hypertrophy both in vivo and in vitro. 3,4 We have been interested in the potential role of the SNS as a mediator of renal injury. It is known that catecholamine infusions can induce acute elevations in glomerular hydrostatic pressure in association with intense renal vasoconstriction and a fall in renal blood flow (RBF). 5,6 Infusions of norepinephrine can also induce microalbuminuria in both normal and diabetic individuals. 7 A combination of intrarenal and i...

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“…20,28 After several weeks of diet, it also occurs the reduction of the peripheral vascular resistance due to the inhibition of sympathetic activity and of the reninangiotensin system. 5,33,34 In addition to the reduction in salt sensitivity and noradrenergic activity, the weight reduction and increased physical activity clearly improve the insulin sensitivity, which may alleviate the mechanisms responsible for the development of hypertension in insulin resistant hypertensive obese subjects. 1,7 It is noteworthy that these bene®cial effects already occur after a partial, moderate loss of weight and are in general associated with the improvement of other cardiovascular risk factors.…”

Section: Therapeutic Conclusionmentioning

confidence: 99%

Obesity and hypertension: from pathophysiology to treatment

Kolanowski

1999

Int J Obes

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While the prevalence of hypertension is clearly increased among the overweight persons, the pathophysiological mechanisms underlying this frequent association of obesity and hypertension are still poorly understood. The expansion of extracellular volume, inducing hypervolaemia and increased cardiac output, represents the characteristic haemodynamic feature of the obesity-related hypertension. The maintenance of hypervolemia in the face of elevated blood pressure, indicates a resetting of pressor natriuresis toward higher blood pressure. The development of hypertension also indicates an increase in peripheral vascular resistance, thus the lack of physiological adaptation of peripheral resistance to increased cardiac output. The mechanisms underlying these changes in renal function and vascular reactivity can no longer be attributed to hyperinsulinaemia as such, but might be related to insulin resistance responsible for the enhancement in pressor activity of noradrenaline and angiotensin II. This increased reactivity to pressor factors may be due to an inadequate nitric oxide generation by vascular endothelium and to increased sodium and calcium concentration in vascular smooth muscle cells. The role of increased neuropeptide Y (NPY) activity, may also be involved. As to enhancement of tubular sodium reabsorption, it could be related to histological changes within the renal medulla, leading to compression of tubules and vasa recta, hence a more ef®cient sodium reabsorption. As to the therapeutic approach, the low-energy sodium-restricted diet associated with increased physical activity, represents the cornerstones of treatment for the obesity-related hypertension. If this approach fails, the pharmacological treatment becomes necessary, and the use of the converting enzyme inhibitors seems to be the most appropriate choice of drug therapy for hypertensive obese patients.

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Role of the Sympathetic Nervous System in Blood Pressure Maintenance in Obesity

Cited by 152 publications

References 24 publications

A Case of Sleep Apnea Syndrome Manifesting Severe Hypertension with High Plasma Norepinephrine Levels

A Case of Sleep Apnea Syndrome Manifesting Severe Hypertension with High Plasma Norepinephrine Levels

Renal Injury and Salt-Sensitive Hypertension After Exposure to Catecholamines

Obesity and hypertension: from pathophysiology to treatment

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