Rapid onset of renal sympathetic nerve activation in rabbits fed a high-fat diet.
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.
Departments of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.
James A
JA
Armitage
Sandra L
SL
Burke
Larissa J
LJ
Prior
Benjamin
B
Barzel
Nina
N
Eikelis
Kyungjoon
K
Lim
Geoffrey A
GA
Head
D050154:Adiposity / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000294:innervation*; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin