Effect of an antihypertensive drug, budralazine, on glucose and lipid metabolism in diabetic SHR

Budralazine was evaluated for its effects on glucose and lipid metabolism in diabetic SHR. SHR treated with 10% sucrose solution as drinking water for 3 months exhibited an impaired glucose tolerance with higher serum insulin levels and a reduction of sigma delta IRI/sigma delta BS. This model was, therefore, considered to resemble hypertensive patients with non-insulin-dependent diabetes (NIDD). Streptozotocin (30 mg/kg, i.v.)-treated SHR had a glucose intolerance with lower serum insulin levels and a reduction of sigma delta IRI/sigma delta BS, suggesting a similarity to hypertensive states with insulin-dependent diabetes (IDD) in humans. Repeated administration of budralazine (15-60 mg/kg/day, p.o.) had no effect on glucose tolerance, insulin secretion, serum electrolytes and lipid levels in Wistar rats, SHR, IDD-SHR and NIDD-SHR. Budralazine caused a significant decrease in systolic blood pressure in IDD-SHR and NIDD-SHR as well as in SHR. Repeated administration of furosemide (50-100 mg/kg/day, p.o.) resulted in a marked reduction in glucose tolerance, sigma delta IRI/sigma delta BS and serum potassium in Wistar rats. These effects of furosemide were more pronounced in SHR and IDD-SHR (IDD-SHR greater than SHR) and were reduced by either KC1 supplement or administration of triamterene. Thus, furosemide-induced glucose intolerance seems, at least partially, to be attributed to potassium loss which led to decreased insulin secretion. From these results, it is possible that budralazine may be useful for the treatment of hypertensive patients with diabetes.