KININS CONTRIBUTE TO THE IMPROVEMENT OF INSULIN SENSITIVITY DURING TREATMENT WITH ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR

Although angiotensin converting enzyme inhibitors and alpha(1)-blocker s have been reported to improve insulin sensitivity, their mechanisms of action have not been elucidated. To investigate the role of kinins in insulin sensitivity, we treated 4-week-old spontaneously hypertensi ve rats with either an angiotensin converting enzyme inhibitor (enalap ril), an alpha(1)-blocker (doxazosin), or an angiotensin II antagonist (losartan) for 3 weeks. A control group received no drugs. In additio n, 18 rats treated with enalapril or doxazosin received a simultaneous administration of a kinin antagonist (Hoe 140). Glucose clamp testing was performed in each group. Enalapril (128+/-1 mm Hg) and doxazosin (132+/-2 mm Hg) decreased mean blood pressure compared with control le vels (148+/-1 mm Hg) (P<.01). The glucose requirement for the clamp te st during the administration of enalapril (25.8+/-0.5 mg/kg per minute ) or doxazosin (28.6+/-0.7 mg/kg per minute) was higher than that of t he control group (19.8+/-0.5 mg/kg per minute) (P<.05). Although Hoe 1 40 did not alter the glucose requirement of doxazosin (27.8+/-0.5 mg/k g per minute), it decreased that of enalapril (22.6+/-0.9 mg/kg per mi nute) (P<.05) without affecting the changes in mean blood pressure ind uced by enalapril. In addition, losartan decreased mean blood pressure but did not affect the glucose requirement. Thus, the improvement in insulin sensitivity produced by an angiotensin converting enzyme inhib itor is mostly dependent on kinins but not on angiotensin II antagonis m, and an alpha(1)-blocker improves insulin sensitivity irrespective o f kinins.