At₁ Receptor Density Changes During Development of Hypertension in Hyperinsulinemic Rats

Abstract

In a previous study we showed that the renin-angiotensin system (RAS) plays a role in the etiology of fructose-induced hypertension. To our knowledge, no previous study has evaluated changes in angiotensin II (Ang II) type I receptor (AT₁) density in fructose-fed rats that are insulin resistant and hypertensive. The purpose of this study was to determine the changes in plasma Ang II and AT₁ density associated with the elevation of blood pressure in fructose-treated rats. Male Sprague-Dawley rats were divided into two groups and were fed either normal rat chow or a 60% fructose-enriched diet for four weeks. Plasma Ang II and serum insulin levels of the fructose-treated rats were significantly elevated (p<0.01) by the end of the second week of fructose treatment. Plasma Ang II levels of the fructose-fed rats returned to basal levels by the end of the fourth week of dietary treatment, whereas the serum insulin levels consistently remained elevated. Blood pressure was significantly elevated in the fructose-fed rats within two weeks of fructose treatment. Elevation of blood pressure was associated with left ventricular hypertrophy. Furthermore, there was a significant increase in AT₁ receptor density in the ventricles and a significant decrease in AT₁ receptor density in the aortas of fructose-fed rats at the end of fourth week. There were no significant changes in receptor density in the hypothalami or adrenal glands of fructose-treated rats. These results suggest that chronic fructose treatment activates the renin-angiotensin system, which is manifested by an increase in plasma Ang II, elevation of blood pressure, cardiac hypertrophy, and changes in AT₁ receptor density.

Key Words:

• Hyperinsulinemia
• insulin resistance
• AT₁ receptor
• hypertension
• renin-angiotensin system