BRADYKININ MAY NOT BE INVOLVED IN IMPROVEMENT OF INSULIN-RESISTANCE BY ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR

We have previously demonstrated that captopril ameliorates glucose int olerance by partially preventing the reduction in postprandial skeleta l muscle blood flow. The present study was designed to clarify the mec hanism by which ACE inhibitors affect glucose metabolism in fructose ( FRU)-fed Wistar rats with hypertension, glucose intolerance and hyperi nsulinemia. Eight-week-old male rats (n=51) were divided into six grou ps. Controls were given a normal chow, while fructose-rich (55%) chow was administered to the remainder for eight weeks. The different group s were administered alacepril (ALA, 30 mg/kg/day) with or without a co ntinuous infusion of Hoe 140, a kinin B-2 receptor antagonist (150 mu g/kg/day), Hoe 140 alone or TCV-116 (1 mg/kg/day), an angiotensin II r eceptor antagonist, alone. After measuring the body weight and systoli c blood pressure (BP), steady-state plasma glucose (SSPG) levels were determined. FRU significantly increased BP from 141 mmHg in controls t o 156 mmHg. ALA with or without Hoe 140 decreased BP to 124 mmHg or 11 7 mmHg, respectively, but Hoe 140 alone did not affect BP. TCV-116 als o decreased BP to 116 mmHg. The SSPG levels increased from 7.58 mM in controls to 8.98 mM in FRU-fed rats. This was lowered with both ALA an d TCV-116. Hoe 140 alone, however, did not affect SSPG levels. Hoe 140 did not show any effects on ALA-induced improvement of SSPG. These re sults suggest that the improvement in glucose tolerance observed with ACE inhibitors is not due to the kinins, and angiotensin II receptor a ntagonists also improve insulin sensitivity.