Abstract 304: A Moderately- Enriched Fructose Diet Increases The Sensitivity Of The Proximal Nephron To Angiotensin II.

Abstract

Consumption of high-fructose corn syrup as a sweetener has been implicated in diabetes, obesity, and hypertension. We have recently shown that a moderately-enriched fructose diet (20%), an amount consumed by more than 30 million Americans, causes salt-sensitive hypertension. Activation of the renin-angiotensin system in the proximal nephron also increases blood pressure presumably due to augmented salt and water reabsorption. However, whether the effects of angiotensin II (Ang II) on proximal tubule transport are enhanced by moderate fructose consumption is unknown. We hypothesize that a diet containing moderate amounts of fructose increases transport in proximal tubules by enhancing their sensitivity to Ang II. To test this, we measured the effects of Ang II on transport-related oxygen consumption (QO2) in proximal tubule suspensions from rats consuming 20% of their calories as fructose in their drinking water for 1 week. We found that 1 pmol/l Ang II stimulated QO2 by tubules from the fructose-fed group but had no effect on those from controls (21 ± 7 vs. 5 ± 3 nmol/mg/min; p < 0.04, n = 7). In contrast, basal QO2 rates were not affected (94 ± 1 vs. 95 ± 4 nmol O2/mg/min, n = 7). Addition of 100 pmol/l Ang II stimulated QO2 to the same extent in both groups (19 ± 8 vs. 18 ± 8 nmol O2/mg/min; n = 7). AT1 receptor mRNA expression in cortical homogenates was not different between groups (8961 ± 454 vs. 8712 ± 575 AU; n = 4). Both groups gained weight at the same rate. We conclude that moderate dietary fructose consumption increases the sensitivity of the proximal nephron to Ang II independently of AT1 expression, and this may contribute to the salt sensitivity of this model.