To determine whether chronic high-fructose feeding causes insulin resistance and hypertension in normal dogs, we fed 10 male dogs a normosodic diet containing 60% of the calories as fructose for 20 to 28 days; a control group of 8 dogs was fed a similar diet containing dextrose instead of fructose. In the fructose-fed group, (1) fasting triglyceridemia increased from 35.3±0.63 to 91.9±11.55 mg/dL after 25 days (f <.001); (2) fasting insulinemia increased from 19.0±1.9 to 58.9±7.22 iU/mL after 25 days (P<.001); (3) insulin resistance, which was estimated by steady-state glycemia during an insulin suppression test, increased from 105.8±21.5 to 187.8±32.6 mg/dL after 15 days (/ > <.001), whereas steady-state insulinemia did not change; (4) mean arterial pressure increased from 100.4±1.6 to 122.6±2.3 mm Hg after 28 days (P<.0l); and (5) cumulative sodium balance was increased on days 7 through 11 (111.60±4.44 mEq on day 8, P<.01), returning to T here is overwhelming epidemiologic evidence that insulin resistance and hyperinsulinemia are strongly associated with hypertension. 1 A constellation of cardiovascular risk factors fostered by insulin resistance, including alterations in the circulating lipidic profile (such as hypertrigryceridemia and hypercholesterolemia with high low-density lipoprotein and low high-density lipoprotein cholesterol), atherosclerosis, and hypertension, has been described and conventionally called "syndrome X." 2 The frequent association between non-insulin-dependent diabetes mellitus, obesity, and hypertension has been tentatively ascribed to the presence of insulin resistance.
-3 However, a marked impairment in insulin action has also been demonstrated in nonobese, nondiabetic essential hypertensive subjects. 4 Insulin resistance and hypertension have been induced in rodents by chronic high-sucrose or highfructose feeding. 5 These models have provided important information regarding the biochemical mechanisms responsible for the impairment of insulin activity. normal for the rest of the experiment. All these parameters were similar between the fructose-fed and dextrose-fed groups before the diets were started and remained constant in the dextrose-fed group. Neither group showed any change in body weight, fasting plasma glucose, atrial natriuretic factor, or endothelin-1 levels. We conclude that chronic high-fructose feeding elicits hypertriglyceridemia, insulin resistance, hyperinsulinemia, hypertension, and a transient sodium retention in dogs without fostering fasting hyperglycemia or weight gain. Endothelin and atrial natriuretic factor do not appear to play a role in the development of hypertension in this model. However, despite these advances, the pathogenic mechanisms that relate insulin resistance to hypertension remain undefined. Most of our knowledge about the homeostatic mechanisms responsible for coupling the renal excretion of sodium to the control of blood volume and blood pressure has been obtained in dogs 7 ; however, to date there have been no available nonobese, ...