From the Graduate Institute of Medical Sciences, Tzu Chi College of
Medicine (W.-C.H.), Division of Nephrology; the Department of Medicine, Tzu
Chi General Hospital (T.-C.F.); and the Department of Pharmacology, College of
Medicine, National Cheng Kung University (J.-T.C.), Taiwan, Republic of China.
AbstractExperiments were performed
to evaluate the role of the renal nerves in
hyperinsulinemia-induced hypertension. Male
Sprague-Dawley rats were made hyperinsulinemic by
insulin infusion via osmotic minipumps implanted subcutaneously (3.0
mU/kg per minute for 6 weeks). Rats with vehicle infusion served as
controls. Bilateral renal denervation was performed either at the
beginning of or 4 weeks after insulin infusion. The systolic
blood pressure was measured by the tail-cuff method twice a week. Food
and water intake and urine flow were measured daily. The results showed
that sustained insulin infusion significantly increased plasma insulin
concentrations from 277.7±25.8 pmol/L to 609.9±22.2 and 696.7±23.0
pmol/L by the end of weeks 4 and 6, respectively
(P<0.05). Systolic blood pressure was
significantly increased from 135±3 to 157±3 and 159±2 mm Hg
(P<0.05) at the corresponding time points. There was a
significant increase in the plasma norepinephrine
concentration after insulin infusion, whereas no significant changes in
plasma triglyceride and glucose concentrations, water
intake, urine flow, sodium excretion, sodium gain, and body weight gain
were observed. Bilateral renal denervation depleted renal
norepinephrine stores and prevented the development of
hyperinsulinemia-induced hypertension. After
hyperinsulinemia-induced hypertension had been
fully established (from 134±2 to 157±2 mm Hg), bilateral renal
denervation reversed the elevated systolic blood pressure to
normotensive levels within 2 weeks. Transient denervated
diuresis and natriuresis were observed. These results indicate
that chronic hyperinsulinemia-induced hypertension
requires the presence of intact renal nerves in rats.
© 1998 American Heart Association, Inc.
Scientific Contributions
Renal Denervation Prevents and Reverses Hyperinsulinemia-Induced Hypertension in Rats
Key Words: hyperinsulinemia insulin resistance renal nerve renal denervation denervated natriuresis
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