Enhanced Adipose Afferent Reflex Contributes to Sympathetic Activation in Diet-Induced Obesity Hypertension

Xiong, Xiao-Qing; Chen, Weiwei; Han, Ying; Zhou, Ye-Bo; Zhang, Feng; Gao, Xing-Ya; Zhu, Guo‐Qing

doi:10.1161/hypertensionaha.112.198002

Cited by 78 publications

(114 citation statements)

References 44 publications

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“…[30][31][32][33][34][35] The lack of correlation between altered BP and HR rhythmicity and TOD in our study may be caused by the fact that absolute BP values in our patients were lower than those reported in studies of adults with hypertension. Second, the exposure to elevated BP is much shorter in adolescents with hypertension than in adults with hypertension.…”

Section: Discussioncontrasting

confidence: 83%

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Blood Pressure Rhythmicity and Visceral Fat in Children With Hypertension

et al. 2013

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M ost biological rhythms are driven by an internal biological clock and can be synchronized by different factors. Blood pressure (BP) is modulated in a circadian 24-hour rhythm. This cycle depends on complex internal factors, including neurogenic and endocrine fluctuations, and external factors such as physical activity and diet. Although the genesis of BP rhythmicity is controversial, an increasing amount of evidence suggests that BP rhythm is generated from oscillators within the central nervous system located in the hypothalamic suprachiasmatic nucleus, either located in discrete pacemaker neurons or originating in neuronal networks.1-3 Additionally, activity of the sympathetic nervous system and the genetic components of the circadian clock may play a fundamental role in the regulation of BP. 2-5Finally, humoral factors (angiotensin, endothelin, NO, bradykinines, insulin) participate in the determination of BP rhythms. 4 Altered circadian BP rhythmicity has been described in many conditions causing increased cardiovascular risk, such as hypertension, chronic kidney disease, diabetes mellitus, and small birth weight. [6][7][8][9] Because the main intermediate phenotype of adolescents with primary hypertension (PH) is visceral obesity and metabolic abnormalities, we hypothesized that normalization of BP along with the decrease of visceral fat would correlate with the normalization of altered BP and heart rate (HR) rhythmicity. Therefore, we evaluated the relationship between BP and HR rhythmicity with target organ damage (TOD) and anthropometrical and metabolic variables in adolescent boys with PH, before and after 1 year of antihypertensive therapy. Patients and MethodsThe study was performed according to the Declaration of Helsinki and with the approval of the Children's Memorial Health Institute Ethics Committee. All patients and parents gave consent to participate in the study.Fifty boys (age, 15.0 years; range, 8.5-17 years) with newly diagnosed PH who underwent all procedures before and after 12 months of standard antihypertensive therapy were included in the study. The exclusion criteria were the following: the presence of any significant chronic disease (except for PH) including diabetes mellitus and chronic kidney disease, any acute illness including infections in the 6 weeks preceding enrollment, and incomplete data. PH was diagnosed according to the fourth Task Force Report and confirmed by 24-hour ambulatory BP monitoring (ABPM). 10 See Editorial Commentary, pp 689-690Abstract-Primary hypertension is associated with disturbed activity of the sympathetic nervous system and altered blood pressure rhythmicity. We analyzed changes in cardiovascular rhythmicity and its relation with target organ damage during 12 months of antihypertensive treatment in 50 boys with hypertension (median, 15.0 years). The following parameters were obtained before and after 12 months of antihypertensive treatment: 24-hour ambulatory blood pressure, left ventricular mass, carotid intima-media thickness, and MRI for visceral ...

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Section: Discussioncontrasting

confidence: 83%

“…34,35 VAT deposition is both the result and the cause of increased sympathetic activity and endocrine disturbances such as hypercortisolism, adipokines secretion, and immune activity. 36 It is also known that insulin resistance is associated with impaired cardiovascular rhythms in humans.…”

Section: Discussionmentioning

confidence: 99%

Blood Pressure Rhythmicity and Visceral Fat in Children With Hypertension

et al. 2013

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“…3 Lidocaine inhibition of neurons in the paraventricular nucleus abolishes the adipose afferent reflex. In high-fat diet obese hypertensive rats, basal-and capsaicin-stimulated afferent nerve activity from white adipose tissue were found to be increased as compared with controls.…”

Section: Obesity-related Hypertensionmentioning

confidence: 99%

Sympathetic Nervous System and Hypertension

2013

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With the development and implementation of device-based therapeutic interventions to decrease renal and systemic nerve activity in patients with resistant hypertension, there has been an increase in research dealing with the role of the sympathetic nervous system in hypertension. These interventions have produced substantial decreases in blood pressure in patients wherein pharmacological treatments, including agents which inhibit the effects of the renin-angiotensin-aldosterone system, have failed serves to confirm and reassert the essential role of the sympathetic nervous system in hypertension. This review will encompass recent publications dealing with the sympathetic nervous system and hypertension, focusing on those recently published in Hypertension. Sympathetic Activation in Animal Models Obesity-Related HypertensionAlthough there has been a debate as to whether sympathetic activation is a cause or consequence of obesity, the studies noted below support the view that it is the obesity that leads to sympathetic activation. The importance of this sympathetic activation for the development of the hypertension is supported by the finding that renal denervation prevents the development of obesity hypertension in the dog.Studies have now focused on the developmental phase of obesity hypertension regarding the renal sympathoexcitation. In rabbits fed high-fat diets, body weight, plasma insulin and leptin concentrations, mean arterial pressure, heart rate, and renal sympathetic nerve activity were all increased after 1 week.1 Mean arterial pressure and body weight continued to increase over 3 weeks of high-fat diet, whereas heart rate and renal sympathetic nerve activity did not change further. Arterial baroreflex control of renal sympathetic nerve activity was attenuated from the first week of the high-fat diet. Excitatory responses to air jet stress diminished over 3 weeks of high-fat diet. Resumption of normal diet normalized glucose, insulin, leptin, and heart rate, but body weight, visceral fat content, mean arterial pressure, and renal sympathetic nerve activity remained elevated. Increased renal sympathetic nerve activity and its impaired baroreflex control, which occur with 1 week of high-fat feeding, seem integral to the rapid development of obesity hypertension. Increased plasma leptin and insulin may contribute to the initiation of hypertension but are not required for maintenance of the hypertension, which is related to the sustained increase in renal sympathetic nerve activity. As the air jet stress response is transduced by hypothalamic neurons, the authors speculate that this site is involved in the maintenance phase of the hypertension with a sustained increase in renal sympathetic nerve activity.The early effects of diet-induced fat accumulation on lumbar sympathetic nerve activity were also examined in rats over 15 days.2 Increases in brown and white adipose tissue (but not body weight) were accompanied by increases in plasma leptin (but not glucose) concentration and heart rate; however, mean a...

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“…It has been demonstrated that the sympathetic activity of obese rats (4,24), renovascular hypertensive rats (5,25,26) and SHRs (6,27,28) is enhanced compared with normotensive rats. Hexamethonium is a ganglionic blocker (10,11) and reduces blood pressure in SHR and Wistar rats (8).…”

Section: A B Cmentioning

confidence: 99%

“…Numerous studies have demonstrated that sympathetic activity is enhanced in patients with essential (1) or secondary hypertension (2,3) in addition to various hypertensive models including obesity (4), renovascular hypertensive rats (5) and spontaneously hypertensive rats (SHRs) (6). Several methods have been used to evaluate sympathetic activity including the cardiac sympathetic afferent reflex (7), the adipose afferent reflex (4), plasma norepinephrine levels (8) and blood pressure response to ganglionic blockade (9).…”

Section: Introductionmentioning

confidence: 99%

Hexamethonium attenuates sympathetic activity and blood pressure in spontaneously hypertensive rats

Gong

Sun

Zhou

et al. 2015

Molecular Medicine Reports

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Abstract. Sympathetic activity is enhanced in heart failure and hypertensive rats. The aims of the current study were: i) To investigate the association between renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to intravenous injection of the ganglionic blocker hexamethonium; and ii) to determine whether normal Wistar rats and spontaneously hypertensive rats (SHRs) differ in their response to hexamethonium. RSNA and MAP were recorded in anaesthetized rats. Intravenous injection of four doses of hexamethonium significantly reduced the RSNA, MAP and heart rate (HR) in the Wistar rats and SHRs. There were no significant differences in the RSNA, MAP or HR between Wistar rats and SHRs at the two lowest doses of hexamethonium. However, the two highest doses of hexamethonium resulted in a greater reduction in the RSNA and MAP in SHRs compared with Wistar rats. There was a significant positive correlation between the alterations in RSNA and MAP in response to the intravenous injection of hexamethonium in the Wistar rats and SHRs. There were no significant differences in the timing of the maximal effects on RSNA, MAP or HR or in recovery following hexamethonium treatment. These results suggest that there is an association between the RSNA and MAP response to intravenous injection of hexamethonium and that the alterations in MAP in response to hexamethonium may be used to evaluate basal sympathetic nerve activity.

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Enhanced Adipose Afferent Reflex Contributes to Sympathetic Activation in Diet-Induced Obesity Hypertension

Cited by 78 publications

References 44 publications

Blood Pressure Rhythmicity and Visceral Fat in Children With Hypertension

Blood Pressure Rhythmicity and Visceral Fat in Children With Hypertension

Sympathetic Nervous System and Hypertension

Hexamethonium attenuates sympathetic activity and blood pressure in spontaneously hypertensive rats

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