Abstract-The activation of the sympathetic nervous system through the central actions of the adipokine leptin has been suggested as a major mechanism by which obesity contributes to the development of hypertension. However, direct evidence for elevated sympathetic activity in obesity has been limited to muscle. The present study examined the renal sympathetic nerve activity and cardiovascular effects of a high-fat diet (HFD), as well as the changes in the sensitivity to intracerebroventricular leptin. New Zealand white rabbits fed a 13.5% HFD for 4 weeks showed modest weight gain but a 2-to 3-fold greater accumulation of visceral fat compared with control rabbits. Mean arterial pressure, heart rate, and plasma norepinephrine concentration increased by 8%, 26%, and 87%, respectively (PϽ0.05), after 3 weeks of HFD. Renal sympathetic nerve activity was 48% higher (PϽ0.05) in HFD compared with control diet rabbits and was correlated to plasma leptin (rϭ0.87; PϽ0.01). Intracerebroventricular leptin administration (5 to 100 g) increased mean arterial pressure similarly in both groups, but renal sympathetic nerve activity increased more in HFD-fed rabbits. By contrast, intracerebroventricular leptin produced less neurons expressing c-Fos in HFD compared with control rabbits in regions important for appetite and sympathetic actions of leptin (arcuate: Ϫ54%, paraventricular: Ϫ69%, and dorsomedial hypothalamus: Ϫ65%). These results suggest that visceral fat accumulation through consumption of a HFD leads to marked sympathetic activation, which is related to increased responsiveness to central sympathoexcitatory effects of leptin. The paradoxical reduction in hypothalamic neuronal activation by leptin suggests a marked "selective leptin resistance" in these animals. (Hypertension. 2010;55:862-868.)Key Words: obesity-related hypertension Ⅲ sympathetic nervous system Ⅲ hypothalamus Ⅲ leptin Ⅲ leptin resistance Ⅲ New Zealand white rabbit O besity is associated with an elevated risk of cardiovascular morbidity and mortality with both clinical and animal studies reporting a strong association between body weight and blood pressure. 1 Several candidate mechanisms are implicated in the development of obesity-related hypertension and include hemodynamic alterations, endothelial dysfunction, impaired renal-pressure natriuresis, and activation of the renin-angiotensin and sympathetic nervous systems (SNS). 2-4 Converging lines of evidence from animals 5,6 and humans 7,8 indicate that obesity is characterized by a marked sympathetic activation. In humans, norepinephrine spillover and sympathetic nerve recording have established a greater sympathetic outflow to the kidneys and skeletal muscle vasculature in obese subjects, whereas cardiac sympathetic nerve activity is reduced. 7-9 Despite these observations, convincing direct evidence for elevated renal sympathetic nerve activity (RSNA) in obesity-related hypertension is lacking, and it is unknown whether SNS activation occurs early in the process or secondary to long-standing obesity...
Intrauterine growth restriction and accelerated postnatal growth predict increased risk of diabetes. Uteroplacental insufficiency in the rat restricts fetal growth but also impairs mammary development and postnatal growth. We used cross fostering to compare the influence of prenatal and postnatal nutritional restraint on adult glucose tolerance, insulin secretion, insulin sensitivity, and hypothalamic neuropeptide Y content in Wistar Kyoto rats at 6 months of age. Bilateral uterine vessel ligation (restricted) to induce uteroplacental insufficiency or sham surgery (control) was performed on d-18 gestation. Control, restricted, and reduced (reducing litter size of controls to match restricted) pups were cross fostered onto a control or restricted mother 1 d after birth. Restricted pups were born small compared with controls. Restricted males, but not females, remained lighter up to 6 months, regardless of postnatal environment. By 10 wk, restricted-on-restricted males ate more than controls. At 6 months restricted-on-restricted males had increased hypothalamic neuropeptide Y content compared with other groups, and together with reduced-on-restricted males had increased retroperitoneal fat weight (percent body weight) compared with control-on-controls. Restricted-on-restricted males had impaired glucose tolerance, reduced first-phase insulin secretion, but unaltered insulin sensitivity, compared with control-on-controls. In males, being born small and exposed to an impaired lactational environment adversely affects adult glucose tolerance and first-phase insulin secretion, but improving lactation partially ameliorates this condition. This study identifies early life as a target for intervention to prevent later diabetes after prenatal restraint.
Abstract-Hypertension and elevated sympathetic drive result from consumption of a high-calorie diet and deposition of abdominal fat, but the etiology and temporal characteristics are unknown. Rabbits instrumented for telemetric recording of arterial pressure and renal sympathetic nerve activity (RSNA) were fed a high-fat diet for 3 weeks then control diet for 1 week or control diet for 4 weeks. Baroreflexes and responses to air-jet stress and hypoxia were determined weekly. After 1 week of high-fat diet, caloric intake increased by 62%, accompanied by elevated body weight, blood glucose, plasma insulin, and leptin (8%, 14%, 134%, and 252%, respectively). Mean arterial pressure, heart rate, and RSNA also increased after 1 week (6%, 11%, and 57%, respectively). Whereas mean arterial pressure and body weight continued to rise over 3 weeks of high-fat diet, heart rate and RSNA did not change further. The RSNA baroreflex was attenuated from the first week of the diet. Excitatory responses to air-jet stress diminished over 3 weeks of high-fat diet, but responses to hypoxia were invariant. Resumption of a normal diet returned glucose, insulin, leptin, and heart rate to control levels, but body weight, mean arterial pressure, and RSNA remained elevated. In conclusion, elevated sympathetic drive and impaired baroreflex function, which occur within 1 week of consumption of a high-fat, high-calorie diet, appear integral to the rapid development of obesity-related hypertension. Increased plasma leptin and insulin may contribute to the initiation of hypertension but are not required for maintenance of mean arterial pressure, which likely lies in alterations in the response of neurons in the hypothalamus. Key Words: sympathetic nervous system Ⅲ obesity Ⅲ rabbits Ⅲ blood pressure Ⅲ heart rate O besity represents a significant risk for cardiovascular disease because of the relationship between excess body fat and hypertension. It is estimated that obesity contributes to hypertension in Ͼ60% of men and women entering the Framingham study.1 The mechanisms underlying this relationship are multifactorial, and for some time there was controversy as to whether the sympathetic nervous system was activated or inhibited in obesity-related hypertension. Bray 2 proposed that obesity was a result of low thermogenic activity secondary to low sympathetic activity, and certainly data from heart rate (HR) variability studies supported this hypothesis. Young and Landsberg 3 hypothesized that sympathetic outflow is increased in obesity to facilitate energy wastage by thermogenesis and to maintain body weight homeostasis, with elevated renal sympathetic activation and hypertension the sequelae. It is now clear that norepinephrine spillover to renal and skeletal muscle beds is increased in obese humans, 4 and microneurographic data indicate that skeletal muscle sympathetic nerve activity is greater in overweight humans, 5 consistent with the observation that sympathetic vasomotor activity in skeletal muscle is elevated in established obesity. 6,7 ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.