Rapid Onset of Renal Sympathetic Nerve Activation in Rabbits Fed a High-Fat Diet

Abstract

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 ...

Sympathetic Nervous System and Hypertension

“…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.…”

Recording sympathetic nerve activity chronically in rats: surgery techniques, assessment of nerve activity, and quantification

“…As an alternative to visually identifying artifacts on traces, some investigators have restricted SNA recordings to a few hours a day when the animals can be monitored for animal movement (1,19,20). This has clear advantages and can provide useful data regarding the disease state and responses to acute experimental manipulations in conscious animals.…”

Exposure to a High-Fat Diet During Development Alters Leptin and Ghrelin Sensitivity and Elevates Renal Sympathetic Nerve Activity and Arterial Pressure in Rabbits

“…4,5 We have recently shown that the renal sympathetic nerve activity (RSNA) and BP increases in the first few days of consuming a high-fat diet (HFD) in rabbits can be largely reversed by a leptin antagonist given intracerebroventricularly (ICV). [6][7][8][9] In contrast, ghrelin secreted by the stomach activates arcuate neurons containing neuropeptide Y and agouti-related protein and has been shown to suppress sympathetic activity, decrease BP, and stimulate appetite.10,11 Thus, both leptin and ghrelin may play a key role in the association between obesity and hypertension and may also be involved in the hypertension programmed by a maternal HFD (m-HFD).The purpose of this study was to examine the effect of an m-HFD during development on arterial pressure and RSNA and the central sympathetic effects of leptin and ghrelin in offspring. We used a rabbit model in which an HFD induces elevated BP and RSNA.…”

“…We used a rabbit model in which an HFD induces elevated BP and RSNA. [6][7][8][9] We hypothesized that offspring exposed to an HFD during development would retain greater deposits of fat and show a selective leptin-resistant phenotype Abstract-Exposure to maternal obesity or a maternal diet rich in fat during development may have adverse outcomes in offspring, such as the development of obesity and hypertension. The present study examined the effect of a maternal high-fat diet (m-HFD) on offspring blood pressure and renal sympathetic nerve activity, responses to stress, and sensitivity to central administration of leptin and ghrelin.…”

“…We used a rabbit model in which an HFD induces elevated BP and RSNA. [6][7][8][9] We hypothesized that offspring exposed to an HFD during development would retain greater deposits of fat and show a selective leptin-resistant phenotype with altered cardiovascular and sympathetic responses to leptin and ghrelin.…”