Effect of antihypertensive treatment with alacepril on insulin resistance in diabetic spontaneously hypertensive rats.
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 effects 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 +/- 7mm 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.
Sato
T
T
Department of Internal Medicine, Shimane Medical University, Izumo, Japan.
Nara
Y
Y
Kato
Y
Y
Yamori
Y
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008076:Cholesterol, HDL / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013311:Streptozocin; D014280:Triglycerides / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D008076:Cholesterol, HDL; D007328:Insulin; D014280:Triglycerides; D013311:Streptozocin; D002216:Captopril; C046835:alacepril