AT(1) RECEPTOR DENSITY CHANGES DURING DEVELOPMENT OF HYPERTENSION IN HYPERINSULINEMIC RATS

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(A ng II) type I receptor (AT(1)) density in fructose-fed rats that are i nsulin resistant and hypertensive. The purpose of this study was to de termine the changes in plasma Ang II and AT(1) density associated with the elevation of blood pressure in fructose-treated rats. Male Spragu e-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 significan tly elevated (p<0.01) by the end of the second week of fructose treatm ent. Plasma Ang II levels of the fructose-fed rats returned to basal l evels by the end of the fourth week of dietary treatment, whereas the serum insulin levels consistently remained elevated. Blood pressure wa s significantly elevated in the fructose-fed rats within two weeks of fructose treatment. Elevation of blood pressure was associated with le ft ventricular hypertrophy. Furthermore, there was a significant incre ase in AT(1) receptor density in the ventricles and a significant decr ease in AT(1) receptor density in the aortas of fructose-fed rats at t he end of fourth week. There were no significant changes in receptor d ensity in the hypothalami or adrenal glands of fructose-treated rats. These results suggest that chronic fructose treatment activates the re nin-angiotensin system, which is manifested by an increase in plasma A ng II, elevation of blood pressure, cardiac hypertrophy, and changes i n AT(1) receptor density.