Affiliation:
1. From the Division of Nephrology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital (T.-C.F.); and the Graduate Institute of Medical Science, Tzu Chi College of Medicine (T.-C.F., W.-C.H.), Hualien, Taiwan, Republic of China.
Abstract
Abstract
—The study was conducted to examine the effects of the angiotensin subtype 1 and 2 receptor antagonists (losartan and
PD123319
, respectively) on blood pressure (BP) and renal excretory function in chronic hyperinsulinemia–induced hypertension in rats. Hyperinsulinemia was achieved by insulin infusion (21.5 pmol/kg per minute) via osmotic minipump for 6 weeks. Losartan or
PD123319
was coinfused either at the beginning or after 4 weeks of insulin infusion. The results showed that insulin infusion significantly increased the plasma insulin concentration from 259.0±22.2 to 646.5±33.0 and 713.9±26.5 pmol/L (
P
<0.05) by the end of the fourth and sixth weeks, respectively, after insulin infusion. There were no significant changes in plasma glucose and triglyceride concentrations. Systolic BP increased from 139±3 to 156±1 and 157±2 mm Hg (
P
<0.05) at the corresponding time points. Combined losartan (3.5 μg/kg per minute) and insulin infusion prevented the rise in BP and improved insulin resistance. When hypertension had been established after 4 weeks of insulin infusion, superimposed infusion of losartan on insulin reversed the elevated BP to control levels within 1 week. In contrast, administration of
PD123319
(0.5 and 10 μg/kg per minute) failed to alter insulin-induced hypertension. Combined
PD123319
with losartan did not alter the losartan-induced hypotensive effect in insulin-infused rats. There were no significant differences in water intake, urine flow, body weight gain, and sodium gain before and after antagonist administration among groups. These results indicate that angiotensin type 1 receptors play a determinant role in the pathogenesis of insulin-induced hypertension in rats.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
32 articles.
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