Hypertension, Vol 23, 450-455, Copyright © 1994 by American Heart Association
H Tomiyama, T Kushiro, H Abeta, T Ishii, A Takahashi, L Furukawa, T Asagami, T Hino, F Saito and Y Otsuka
Although angiotensin converting enzyme inhibitors and alpha 1-blockers 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 hypertensive rats with
either an angiotensin converting enzyme inhibitor (enalapril), an alpha
1-blocker (doxazosin), or an angiotensin II antagonist (losartan) for 3
weeks. A control group received no drugs. In addition, 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 mmHg) and doxazosin (132 +/- 2 mmHg) decreased mean
blood pressure compared with control levels (148 +/- 1 mmHg) (P < .01).
The glucose requirement for the clamp test 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 the control group (19.8 +/- 0.5 mg/kg
per minute) (P < .05). Although Hoe 140 did not alter the glucose
requirement of doxazosin (27.8 +/- 0.5 mg/kg per minute), it decreased that
of enalapril (22.6 +/- 0.9 mg/kg per minute) (P < .05) without affecting
the changes in mean blood pressure induced 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 inhibitor is mostly dependent on kinins but
not on angiotensin II antagonism, and an alpha 1-blocker improves insulin
sensitivity irrespective of kinins.
ARTICLES
Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor
Department of Cardiology, Surugadai Nihon University Hospital, Tokyo, Japan.
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