Effect of antihypertensive treatment with alacepril on insulin resistance in diabetic spontaneously hypertensive rats

Sato, Toshiaki; Nara, Yasuo; Kato, Yuzuru; Yamori, Yukio

« Previous Next »Metabolism - Clinical and Experimental
Volume 45, Issue 4 , Pages 457-462, April 1996

Effect of antihypertensive treatment with alacepril on insulin resistance in diabetic spontaneously hypertensive rats

Toshiaki Sato
- Address reprint requests to Toshiaki Sato, MD, PhD, First Division, Department of Internal Medicine, Shimane Medical University, Izumo 693, Japan.
- Department of Internal Medicine, Shimane Medical University, IzumoJapan
- Otsuka Department of International Nutritional Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan
Yasuo Nara
- Department of Internal Medicine, Shimane Medical University, IzumoJapan
- Otsuka Department of International Nutritional Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan
Yuzuru Kato
- Department of Internal Medicine, Shimane Medical University, IzumoJapan
- Otsuka Department of International Nutritional Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan
Yukio Yamori
- Department of Internal Medicine, Shimane Medical University, IzumoJapan
- Otsuka Department of International Nutritional Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan

Received 10 April 1995; accepted 24 September 1995.

Abstract

Recent clinical reports have described the close relationship between insulin resistance and hypertension. Previous reports from our laboratory documented that spontaneously hypertensive rats (SHR) have mild insulin resistance, and that this insulin resistance is more intense in SHR with diabetes induced by streptozotocin (STZ). The aim of this study was to elucidate the effect of antihypertensive treatment with alacepril on insulin resistance in these diabetic SHR. Animals were divided into four groups as follows: group A, nondiabetic SHR; group B, diabetic SHR; group C, diabetic SHR treated with 0.05% alacepril; and group D, diabetic SHR treated with 0.1% alacepril. Diabetes was induced by intravenous (IV) injection of STZ (35 mg/kg bodyweight [BW]). Alacepril was given orally by mixing in laboratory chow. Mean (±SD) blood pressure was lowered in the alacepril-treated groups (A 212 ± 7 mm Hg and B 213 ± 8 v C 184 ± 6 and D 167 ± 9; P < .01). Total integrated plasma glucose levels were different among all the groups by oral glucose tolerance test (OGTT) (B 53.6 ± 3.3 mmol/L > C47.2 ± 4.5 > D 42.3 ± 1.4 > A 34.2 ± 1.2; P < .01). Steady-state plasma glucose (SSPG) during the insulin suppression test was higher in group B than in group A (15.7 ± 1.5 mmol/L v 10.4 ± 0.8; P < .001). The SSPG level (12.9 ± 0.7) was significantly (P < .001) lower in group D than in untreated group B. In the diabetic groups, blood pressure was positively correlated with integrated plasma glucose (PG) (r = .79, P < .001), SSPG (r = .53, P < .02), and plasma triglyceride (r = .70, P < .001), and negatively with high-density lipoprotein (HDL)-cholesterol (r = −.74, P < .001). Alacepril treatment not only dose-relatedly lowered mean blood pressure, but also dose-relatedly improved abnormalities in carbohydrate and lipid metabolism in STZ-induced diabetic SHR. These results suggest that an angiotensin-converting enzyme inhibitor, alacepril, has an antihypertensive effect, but also improves insulin resistance in hypertension with diabetes mellitus.