The contribution of skeletal muscle tumor necrosis factor-alpha to insulinresistance and hypertension in fructose-fed rats

Objective The aim of this study was to determine the role of tumor necrosis factor-alpha (TNF-alpha) in skeletal muscle tissue in insulin resistance a nd hypertension and the effect of anti-hypertensive medicine on skeletal mu scle TNF-alpha in fructose-induced insulin-resistant and hypertensive rats (fructose-fed rats: FFR). Design and methods Six-week-old male Sprague-Dawley rats were fed either no rmal rat chow or fructose-rich chow. For the last 2 weeks of a 6-week perio d of either diet, the rats were treated with a vehicle (control or FFR); te mocapril, an angiotensin converting enzyme inhibitor (ACEI); or CS-866, an angiotensin II type 1 receptor blocker (ARB). The euglycemic hyperinsulinem ic glucose clamp technique was performed to evaluate insulin sensitivity (M value), TNF-alpha levels in soleus and extensor digitorum longus (EDL) mus cles and epididymal fat pads were measured. We also measured the TNF-alpha concentration in an incubated medium secreted from soleus muscle strips wit h or without angiotensin II. Results TNF-alpha levels were significantly higher in the soleus and EDL mu scles, but not in the epididymal fat, in the FFRs compared with the control rats. Temocapril and CS-866 lowered systolic blood pressure, improved insu lin resistance, and reduced TNF-alpha in both skeletal muscles. There were significant negative correlations between M values and TNF-alpha levels in both soleus and EDL muscles, Also, the soleus muscle strip incubation with 10(-7) mol/l angiotensin II increased TNF-alpha secreted into the incubatio n medium compared to the incubation without angiotensin II. These results s uggest that skeletal muscle TNF-alpha is linked to insulin resistance and h ypertension and that angiotensin II may be one of the factors that regulate skeletal muscle TNF-alpha. J Hypertens 18:1605-1610 (C) 2000 Lippincott Wi lliams & Wilkins.