Impact of High‐Fructose Consumption on the Canine Cardiovascular System

Abstract

Many studies have shown the correlation between fructose consumption (FC) and detrimental effects on the cardiovascular system. We hypothesized that the effects of FC are mediated by an overactivation of NADPH oxidase (Nox), which increases superoxide (O2−) production, effectively reducing NO bioavailability. We explored this hypothesis using male mongrel dogs (N=6) fed 60% fructose diet for 49 days. Hemodynamic measurements and echocardiography showed increases in blood pressure (122±1/81±3 to 157±3/117±7 mmHg) with no significant changes in coronary blood flow, shortening fraction, left ventricular pressure, or dP/dt. Furthermore, though no significant changes were seen in stroke volume or cardiac output, total peripheral resistance was significantly increased (36 ± 4 to 60 ± 7 mmHg). Preliminary data also showed an increase in glucose, lactate, and O2 uptake by the heart and a temporal increase in plasma insulin and Ang II. The ability of bradykinin to reduce myocardial O2 consumption ex vivo was impaired by FC, an effect reversed by apocynin or tiron, a Nox inhibitor and O2− scavenger, respectively. Finally, quantification of O2− by lucigenin chemiluminescence showed a significant increase of O2− in FC heart. In conclusion, FC lowers NO bioavailability through the generation of O2−, which alters the control of arterial pressures and disrupts the metabolism of the normal myocardium. Supported by PO43023.