The role that the central sympathetic nervous system plays in the developme
nt of obesity hypertension and insulin was evaluated by feeding dogs a high
fat diet with or without clonidine treatment. Thirteen adult mongrel dogs
were chronically instrumented and randomly assigned to receive either a hig
h fat diet and no clonidine (n=6) or a high fat diet plus clonidine (n=7),
0.3 mg BID. Blood pressure, heart rate, plasma insulin, and electrolytes we
re measured daily. Insulin resistance was assessed with a multiple-dose eug
lycemic clamp (1, 2, and 30 mU.kg(-1).min(-1)) before and after 1, 3, and 6
weeks of the high fat diet. Clonidine prevented the hypertension, tachycar
dia, and insulin resistance associated with feeding dogs the high fat diet
but did not affect weight gain. The present study suggests that the central
sympathetic nervous system plays a critical role in the development of bot
h insulin resistance and hypertension associated with feeding dogs a high f
at diet.