Effects of Hyperinsulinemia on Blood Pressure in High-Fat Diet Fed Rats

Abstract

Objective. To determine the mechanisms of hyperinsulinemia-induced elevation in blood pressure in rats. Methods. Male Sprague-Dawley rats were divided into normal diet (normal control) and high-fat diet group. After 36 weeks of feeding, high-fat diet group was further randomized into high-fat diet control group and streptozocin treatment group. Plasma insulin, endothelin-1(ET-1), norepinephrine (NE), aldosterone, and angiotensin II levels were measured. AT1 receptor, ET-1, and ETA receptor mRNA expression in the aorta was evaluated by real-time PCR. Results. After 9 months, systolic blood pressure (SBP) in high-fat diet group was higher than in the normal control group (155.4±1.6 vs.132.1±5.3 mmHg, P<0.01). The levels of plasma insulin in high-fat diet group were higher than in normal control group (116.63±12.31μIU/mL versus 29.10±4.92μIU/mL, P<0.01). High-fat diet group also exhibited higher plasma levels of ET-1, NE, aldosterone, and angiotensin II,and a lower 24 h urinary sodium excretion than the normal control group (P<0.05). The expression of AT1 receptor, ET-1 and ETA receptors in the aorta in the high-fat diet group was greater than in the normal control group (P<0.05). Streptozocin treatment reduced SBP by an average of 20.9±3.3 mmHg (P<0.05), and reduced insulin level from 110.63±14.86μIU/mL to 39.45±6.59μIU/mL (P<0.01). The streptozocin group also showed a higher level of urine sodium excretion, and a lower level of plasma ET-1 and NE than in the high-fat diet control group (P<0.05). Conclusions. Hyperinsulinemia following high-fat diet is associated with an elevation in blood pressure. Sodium retention, increased plasma endothelin-1 and noradrenaline, as well as activation of renin-angiotensin system may all contribute to the blood pressure elevation.