The contribution of skeletal muscle tumor necrosis factor-α ... : Journal of Hypertension (original) (raw)

Original article

The contribution of skeletal muscle tumor necrosis factor-α to insulin resistance and hypertension in fructose-fed rats

Togashi, Nobuhiko1,2; Ura, Nobuyuki1; Higashiura, Katsuhiro1; Murakami, Hideyuki1; Shimamoto, Kazuaki1

12nd Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.

2Correspondence and requests for reprints to: Nobuhiko Togashi M.D., 2nd Department of Internal Medicine, Sapporo Medical University School of Medicine, S1W16, Chuo-ku, Sapporo 060-8543, Japan. Tel: +81 11 611 2111; fax: +81 11 644 7958; e-mail: [email protected]

Received 23 May 2000 Revised 24 July 2000 Accepted 28 July 2000

Abstract

Objective

The aim of this study was to determine the role of tumor necrosis factor-α (TNF-α) in skeletal muscle tissue in insulin resistance and hypertension and the effect of anti-hypertensive medicine on skeletal muscle TNF-α 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 normal rat chow or fructose-rich chow. For the last 2 weeks of a 6-week period of either diet, the rats were treated with a vehicle (control or FFR); temocapril, an angiotensin converting enzyme inhibitor (ACEI); or CS-866, an angiotensin II type 1 receptor blocker (ARB). The euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity (M value). TNF-α levels in soleus and extensor digitorum longus (EDL) muscles and epididymal fat pads were measured. We also measured the TNF-α concentration in an incubated medium secreted from soleus muscle strips with or without angiotensin II.

Results

TNF-α levels were significantly higher in the soleus and EDL muscles, but not in the epididymal fat, in the FFRs compared with the control rats. Temocapril and CS-866 lowered systolic blood pressure, improved insulin resistance, and reduced TNF-α in both skeletal muscles. There were significant negative correlations between M values and TNF-α levels in both soleus and EDL muscles. Also, the soleus muscle strip incubation with 10−7 mol/l angiotensin II increased TNF-α secreted into the incubation medium compared to the incubation without angiotensin II. These results suggest that skeletal muscle TNF-α is linked to insulin resistance and hypertension and that angiotensin II may be one of the factors that regulate skeletal muscle TNF-α.