Sympathetic Mechanisms, Organ Damage, and Antihypertensive Treatment

Seravalle, Gino; Dell’Oro, Raffaella; Mancia, Giuseppe

doi:10.1007/s11906-011-0200-4

Cited by 46 publications

(47 citation statements)

References 41 publications

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“…The adrenergic activation, albuminuria, and a decreased glomerular filtration rate (GFR) display an adverse impact on cardiovascular morbidity and mortality in CKD patients [7,8]. Besides extrarenal effects, sympathetic overactivity influences renal sodium excretion and reabsorption, renal perfusion, glomerular filtration rate, and renin release [9,10]. Moreover, increased activity of the sympathetic nervous system is associated with estimated glomerular filtration rate (eGFR) and proteinuria suggesting that the activation of this system is a progression factor in CKD patients [11].…”

Section: Introductionmentioning

confidence: 99%

Impact of Baroreflex Activation Therapy on Renal Function - A Pilot Study

Wallbach¹,

Lehnig²,

Schroer

et al. 2014

Am J Nephrol

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Background/Aims: Resistant hypertension and chronic kidney disease (CKD) are interlinked via sympathetic overdrive. Baroreflex activation therapy (BAT) has been shown to chronically reduce blood pressure (BP) in patients with resistant hypertension. The effect of BAT on renal function in CKD patients with resistant hypertension has not been reported. The aim of this study was to investigate the effect of sympathetic inhibition on renal function in CKD patients. Methods: 23 CKD patients with resistant hypertension were prospectively treated with BAT. Analyses were performed before and 6 months after the start of BAT. The renal function was analyzed by creatinine, cystatin C, glomerular filtration rate (GFR), renin, aldosterone, fractioned and 24-hour sodium excretion and analyses of urine marker proteins. The purpose of the control group was to investigate the influence of treating patients in a center for hypertension and regression to the mean on investigated variables. Results: The office mean BP decreased from 116.9 ± 20.9 mm Hg to 104.2 ± 22.2 mm Hg (p < 0.01), while the number of prescribed antihypertensive classes decreased from 6.6 ± 1.6 to 6.1 ± 1.7 (p = 0.02). Proteinuria and albuminuria decreased from a median of 283.9 and 47.7 to 136.5 (p = 0.01) and 45.0 mg/g creatinine (p = 0.01) with pronounced effects in higher CKD stage III + IV compared to I + II (p < 0.01). CKD-EPI cystatin C equation improved from 53.6 ± 22.7 to 60.4 ± 26.1 ml/min (p = 0.02). While creatinine and GFR were impaired after a period of 6 months, no changes of proteinuria, albuminuria, or BP were obtained in control patients. Conclusion: The data of this prospective trial demonstrate potential nephroprotective effects of BAT in therapy-resistant hypertension in CKD patients by a reduction of BP, proteinuria and moreover, a stabilization of estimated GFR.

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Section: Introductionmentioning

confidence: 99%

Impact of Baroreflex Activation Therapy on Renal Function - A Pilot Study

Wallbach¹,

Lehnig²,

Schroer

et al. 2014

Am J Nephrol

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“…[1][2][3][4] SNS activation is mainly regulated by the brain, [5][6][7] and we have demonstrated in rat models with hypertension or heart failure that direct interventions to the brain have beneficial effects because of sympathoinhibition. [8][9][10][11][12][13][14] Particularly in the brain, SNS activation is mainly regulated by the rostral ventrolateral medulla (RVLM) in the brainstem, and the functional integrity of the RVLM is essential for the maintenance of basal vasomotor tone.…”

Section: Introductionmentioning

confidence: 99%

Sympathoinhibition caused by orally administered telmisartan through inhibition of the AT1 receptor in the rostral ventrolateral medulla of hypertensive rats

2012

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In patients and animals with hypertension, sympathetic nervous system (SNS) activation is present. We have demonstrated that angiotensin II type 1 receptor (AT 1 R)-induced oxidative stress in the rostral ventrolateral medulla (RVLM), a vasomotor center in the brainstem, causes SNS activation in hypertensive rats. The aim of the present study was to determine whether orally administered AT 1 R blockers (ARBs) inhibit SNS activation through an anti-oxidant effect via inhibition of AT 1 R in the RVLM of hypertensive rats and, if so, whether the benefits are class effects of ARBs. Stroke-prone spontaneously hypertensive rats (SHRSPs), a hypertensive model with sympathoexcitation, were divided into four groups: SHRSPs treated with telmisartan (TLM), candesartan (CAN), or hydralazine (HYD) and a vehicle group (VEH). Although systolic blood pressure was reduced in the TLM, CAN and HYD groups to the same level, heart rate, SNS activation and oxidative stress in the RVLM were significantly lower in the TLM group only. The pressor effect caused by the microinjection of angiotensin II into the RVLM and the depressor effect caused by the microinjection of tempol, a superoxide dismutase mimetic, into the RVLM were both significantly smaller in TLM, but not in CAN or HYD. These results suggest that orally administered TLM inhibits SNS activation through an anti-oxidant effect via inhibition of AT 1 R in the RVLM of SHRSPs; these results are also independent of depressor effects and are not class effects of ARBs. Keywords: angiotensin II; brain; oxidative stress; sympathetic nervous system INTRODUCTION Sympathetic nervous system (SNS) activation is a main cause of the development and progression of hypertension. 1-4 SNS activation is mainly regulated by the brain, 5-7 and we have demonstrated in rat models with hypertension or heart failure that direct interventions to the brain have beneficial effects because of sympathoinhibition. [8][9][10][11][12][13][14] Particularly in the brain, SNS activation is mainly regulated by the rostral ventrolateral medulla (RVLM) in the brainstem, and the functional integrity of the RVLM is essential for the maintenance of basal vasomotor tone. 5,6 We have demonstrated that oxidative stress in the RVLM produced by the angiotensin II type 1 receptor (AT 1 R) causes SNS activation. 11,14-17 Upregulation of the central AT 1 R is important in the pathophysiology of hypertension. 6,7 Microinjection of AT 1 R blockers (ARBs) into the RVLM or intracerebroventricular infusion of ARBs inhibits SNS activation in hypertensive rats. 15,[18][19][20] However, AT 1 R or oxidative stress in the RVLM have not been targets for the treatment of hypertensive patients because we do not have suitable oral agents to inhibit AT 1 R or oxidative stress in the RVLM of hypertensive patients.

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“…In virtually all experimental models, the increase in ventricular wall thickness is associated with increased sympathetic cardiac drive. Chronic systemic infusion of NE induces ventricular hypertrophy, whereas both α-blockade and sympathectomy can reduce the fi brosis associated with myocardial hypertrophy [ 19 ].…”

Section: Sns Hyperactivity and Target-organ Damagementioning

confidence: 99%

Sympathetic and Renin–Angiotensin Activity in the Pathophysiology of Hypertension

Covic

Segall

2015

Pathophysiology and Pharmacotherapy of Cardiovascular Disease

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The implication of the sympathetic nervous system (SNS) in the pathogenesis of essential hypertension has been suggested a long time ago, considering the major role played by this system in blood pressure (BP) regulation. Studies based on both global (e.g., plasma norepinephrine) and regional (norepinephrine spillover and microneurography) assessments of sympathetic activity have demonstrated that neurogenic mechanisms may be involved in up to 50 % of all cases of essential hypertension. In addition, renal sympathetic denervation has been shown to induce signifi cant and persistent decreases in BP. Moreover, there is evidence that sympathetic hyperactivity may contribute directly to target-organ damage, including cardiac hypertrophy, vascular remodeling, and renal dysfunction. The specifi c causes of sympathetic activation in essential hypertension are not entirely known, but genetic factors, high dietary salt intake, as well as several metabolic and neurohumoral abnormalities have been involved. In patients with obesity-and metabolic syndrome-associated hypertension, SNS overactivity may result from many factors, including hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, hypoghrelinemia, and RAAS activation.The renin-angiotensin system (RAS) is another key regulator of BP and fl uid homeostasis. Ang II induces BP elevation by vasoconstriction of renal and systemic arterioles, stimulation of renal tubular sodium reabsorption, and release of aldosterone from the adrenal glands. Moreover, both Ang II (via AT 1 receptors) and aldosterone exert proinfl ammatory, profi brotic, and prooxidant effects on the cardiovascular system, contributing to myocardial hypertrophy and fi brosis, vascular remodeling and calcifi cation, cerebrovascular damage, and renal glomerular and tubulointerstitial injury. In contrast, other components of the RAS, including mainly the AT 2 receptors and the ACE2/Ang-(1-7)/Mas axis, counteract most of the negative cardiovascular effects of the Ang II/AT 1 /aldosterone system and might play a compensatory role in hypertension.

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Sympathetic Mechanisms, Organ Damage, and Antihypertensive Treatment

Cited by 46 publications

References 41 publications

Impact of Baroreflex Activation Therapy on Renal Function - A Pilot Study

Impact of Baroreflex Activation Therapy on Renal Function - A Pilot Study

Sympathoinhibition caused by orally administered telmisartan through inhibition of the AT1 receptor in the rostral ventrolateral medulla of hypertensive rats

Sympathetic and Renin–Angiotensin Activity in the Pathophysiology of Hypertension

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