Obesity-Induced Hypertension: Brain Signaling Pathways

Carmo, Jussara M. do; Silva, Alexandre A. da; Wang, Zhen; Fang, Taolin; Aberdein, Nicola; Rodriguez, Cecilia E. P. de Lara; Hall, John E.

doi:10.1007/s11906-016-0658-1

Cited by 50 publications

(31 citation statements)

References 88 publications

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“…An increase in serum osmolarity by salt has been shown to activate the aldose reductase-fructokinase pathway in the liver and hypothalamus that can over time lead to metabolic syndrome and elevations in blood pressure [3]. The increase in serum and SNS osmolarity stimulates vasopressin and leptin release [34], and the latter can activate the SNS sympathetic response to raise blood pressure [35]. An increase in SNS osmolarity also stimulates the production of cardiotonic steroids (Na-K ATPase) inhibitors that cause peripheral vasoconstriction [36].…”

Section: Discussionmentioning

confidence: 99%

Hyperosmolarity and Increased Serum Sodium Concentration Are Risks for Developing Hypertension Regardless of Salt Intake: A Five-Year Cohort Study in Japan

et al. 2020

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The potential contribution of serum osmolarity in the modulation of blood pressure has not been evaluated. This study was done to examine the relationship between hyperosmolarity and hypertension in a five-year longitudinal design. We enrolled 10,157 normotensive subjects without diabetes who developed hypertension subsequently as determined by annual medical examination in St. Luke’s International Hospital, Tokyo, between 2004 and 2009. High salt intake was defined as >12 g/day by a self-answered questionnaire and hyperosmolarity was defined as >293 mOsm/L serum osmolarity, calculated using serum sodium, fasting blood glucose, and blood urea nitrogen. Statistical analyses included adjustments for age, gender, body mass index, smoking, drinking alcohol, dyslipidemia, hyperuricemia, and chronic kidney disease. In the patients with normal osmolarity, the group with high salt intake had a higher cumulative incidence of hypertension than the group with normal salt intake (8.4% versus 6.7%, p = 0.023). In contrast, in the patients with high osmolarity, the cumulative incidence of hypertension was similar in the group with high salt intake and in the group with normal salt intake (13.1% versus 12.9%, p = 0.84). The patients with hyperosmolarity had a higher incidence of hypertension over five years compared to that of the normal osmolarity group (p < 0.001). After multiple adjustments, elevated osmolarity was an independent risk for developing hypertension (OR (odds ratio), 1.025; 95% CI (confidence interval), 1.006–1.044), regardless of the amount of salt intake. When analyzed in relation to each element of calculated osmolarity, serum sodium and fasting blood glucose were independent risks for developing hypertension. Our results suggest that hyperosmolarity is a risk for developing hypertension regardless of salt intake.

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Section: Discussionmentioning

confidence: 99%

Hyperosmolarity and Increased Serum Sodium Concentration Are Risks for Developing Hypertension Regardless of Salt Intake: A Five-Year Cohort Study in Japan

et al. 2020

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“…63 In contrast, RDN has been shown to be highly effective in reducing BP in obesity-induced HT which is associated with increased RSNA and may account for 65-75% of the risk for primary HT as well being a major contributor to treatment resistant HT. 8,21,42,[138][139][140][141] The drugs used to treat HT may also influence BP responses to RDN. Experimental studies indicate that the effects of increased RSNA on kidney function are mediated via direct αadrenergic stimulation of tubular NaCl reabsorption as well as β-adrenergic stimulation of renin release and subsequent ANG II formation which, in turn, has multiple effects to increase NaCl reabsorption.…”

Section: In Which Patients Is Rdn Most Likely To Effectively Reduce Bp?mentioning

confidence: 99%

Device-Based Neuromodulation for Resistant Hypertension Therapy

Lohmeier

Hall

2019

Circulation Research

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Despite availability of effective drugs for hypertension therapy, significant numbers of hypertensive patients fail to achieve recommended blood pressure (BP) levels while on ≥3 antihypertensive drugs of different classes. These individuals have a high prevalence of adverse cardiovascular events and are defined as having resistant hypertension (RHT) although nonadherence to prescribed antihypertensive medications is common in patients with apparent RHT. Furthermore, apparent and true RHT often display increased sympathetic activity. Based on these findings, technology was developed to treat RHT by suppressing sympathetic activity with electrical stimulation of the carotid baroreflex and catheter-based renal denervation (RDN). Over the last 15 years, experimental and clinical studies have provided better understanding of the physiological mechanisms that account for BP lowering with baroreflex activation (BA) and RDN and, in so doing, have provided insight into which patients in this heterogeneous hypertensive population are most likely to respond favorably to these device-based therapies. Experimental studies have also played a role in modifying device technology after early clinical trials failed to meet key endpoints for safety and efficacy. At the same time, these studies have exposed potential differences between BA and RDN and common challenges that will likely impact antihypertensive treatment and clinical outcomes in patients with RHT. In this review, we emphasize physiological studies that provide mechanistic insights into BP lowering with BA and RDN in the context of progression of clinical studies, which are now at a critical point in determining their fate in RHT management.

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“…A large number of preclinical investigations have identified the central pathways involved in regulating sympathetic outflow in obesity (for a comprehensive review, see Refs. [38][39][40]. While the central regulation of sympathetic outflow in obesity is undoubtedly complex, involving multiple pathways and neurotransmitter systems, a number of studies have demonstrated the importance of the hypothalamic leptin−melanocortin system in sympathetic regulation in models of obesity, with α-melanocortin−stimulating hormone being particularly effective in stimulating renal sympathetic nerve activity in high-fat fed rabbits.…”

Section: Central Regulation Of Sympathetic Activity In Obesitymentioning

confidence: 99%

Sympathetic activity in obesity: a brief review of methods and supportive data

Lambert

Schlaich

Eikelis

et al. 2019

Annals of the New York Academy of Sciences

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The increase in the prevalence of obesity and the concomitant rise in obesity-related illness have led to substantial pressure on health care systems throughout the world. While the combination of reduced exercise, increased sedentary time, poor diet, and genetic predisposition is undoubtedly pivotal in generating obesity and increasing disease risk, a large body of work indicates that the sympathetic nervous system (SNS) contributes to obesity-related disease development and progression. In obesity, sympathetic nervous activity is regionalized, with activity in some outflows being particularly sensitive to the obese state, whereas other outflows, or responses to stimuli, may be blunted, thereby making the assessment of sympathetic nervous activation in the clinical setting difficult. Isotope dilution methods and direct nerve recording techniques have been developed and utilized in clinical research, demonstrating that in obesity there is preferential activation of the muscle vasoconstrictor and renal sympathetic outflows. With weight loss, sympathetic activity is reduced. Importantly, sympathetic nervous activity is associated with end-organ dysfunction and changes in sympathetic activation that accompany weight loss are often reflected in an improvement of end-organ function. Whether targeting the SNS directly improves obesity-related illness remains unknown, but merits further attention.

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Obesity-Induced Hypertension: Brain Signaling Pathways

Cited by 50 publications

References 88 publications

Hyperosmolarity and Increased Serum Sodium Concentration Are Risks for Developing Hypertension Regardless of Salt Intake: A Five-Year Cohort Study in Japan

Hyperosmolarity and Increased Serum Sodium Concentration Are Risks for Developing Hypertension Regardless of Salt Intake: A Five-Year Cohort Study in Japan

Device-Based Neuromodulation for Resistant Hypertension Therapy

Sympathetic activity in obesity: a brief review of methods and supportive data

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