The effects of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist on insulin resistance in fructose-fed rats

The aim of this study was to compare the effects of an angiotensin-converti ng enzyme (ACE) inhibitor and an angiotensin II receptor (AT) antagonist on insulin resistance, especially on muscle fiber composition in fructose-ind uced insulin-resistant and hypertensive rats. Six-week-old male Sprague-Daw ley rats were fed either normal rat chow (control) or a fructose-rich diet (FFR). For the last two weeks of a six-week period of either diet, the rats were treated with gum arabic solution as a vehicle (control or FFR), angio tensin-converting enzyme inhibitor (FFR+ACE), temocapril (1 mg/kg/day) or a n angiotensin II receptor antagonist (FFR+AT), CS-866 (0.3 mg/kg/day), by g avage, and then the euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity. At the end of the glucose clamp , the soleus muscle was dissected for determination of the muscle fiber com position by ATPase methods. Blood pressure at the glucose clamp in the FFR group was significantly higher than that of the control group, and both tem ocapril and CS-866 significantly lowered the blood pressure of the EFR grou p. The average rate of glucose infusion during the glucose clamp, as a meas ure of insulin sensitivity (M value), was significantly lower in the FFR ra ts compared to the controls (15.4 +/- 0.4, 10.9 +/- 0.6 mg/kg/min, for cont rol and FFR, respectively, P < .01). Both temocapril and CS-866 partially i mproved the M values compared to FFR (13.2 +/- 0.7, 12.8 +/- 0.5 mg/kg/min, for FFR+ACE, FFR+AT, respectively, P < .01 compared with FFR, P < .05 comp ared with control). The composite ratio of type I fibers of the soleus musc le was decreased significantly in the FFR rats compared with the controls ( 82% +/- 2%, 75% +/- 2%, for control and FFR, respectively, P < .01), and bo th temocapril and CS-866 restored a composite ratio of type I fibers to the same level as that of the controls (81% +/- 1%, 80% +/- 1% for FFR+ACE and FFR+AT, respectively). The M value was significantly correlated with the c omposition of type I and type II fibers. These results suggest that the fib er composition of skeletal muscle is correlated to insulin resistance, and that both ACE inhibitors and AT antagonists may modulate the muscle fiber c omposition in a hypertensive and insulin-resistant animal model, fructose-f ed rats, to the same extent. Am J Hypertens 2000;13:290-297 (C) 2000 Americ an Journal of Hypertension, Ltd.