Poor Glycemic Control Induces Hypertension in Diabetes Mellitus

Abstract

We conducted this study to test the hypothesis that hypertension is a primary consequence of poor glycemic control per se very early in insulin-dependent diabetes mellitus. Sprague-Dawley rats (n=15) were instrumented with artery and vein catheters, placed in metabolic cages, and sodium intake was clamped throughout the study. Mean arterial pressure was measured 24 h/d. After a precontrol period, streptozotocin (70 mg/kg IV) was administered, and 15 hours later a continuous intravenous infusion was begun at 4 U/rat per day. The insulin infusion was titrated on an individual rat basis to maintain good glycemic control, and after this 7-day control period, blood glucose, urinary sodium excretion, and mean arterial pressure were not different from precontrol values, averaging 8.8 +/- 0.6 mmol/L, 2.8 +/- 0.2 mmol/d, and 103 +/- 2 mm/Hg, respectively, for control days 5 through 7. Subsequently, a 4-day period of poor glycemic control was initiated by reducing the insulin infusion rate. Blood glucose, urinary sodium excretion, and mean arterial pressure began to increase on day 1; for diabetes days 3 and 4, they averaged 23.4 +/- 1.0 mmol/L, 3.6 +/- 0.1 mmol/d, and 110 +/- 2 mm Hg, respectively. All were significantly elevated. When insulin treatment was restored, all variables returned to control levels during the next 4 days. A second 4-day diabetic period yielded similar results. These results indicate that elevated blood pressure is a primary consequence of poor glycemic control in insulin-dependent diabetes, occurring before renal injury has had time to develop, and therefore, may be a factor contributing to the initiation of end-organ injury.

The relationship between blood pressure and sciatic nerve blood flow velocity in rats with insulin-treated experimental diabetes

“…51,52 However, using direct methods, it has been established that the insulin treatment augments blood pressure in rats with experimental diabetes. 35,36 More importantly, in this study, the rats were not severely hyperglycaemic and their tails were not emaciated. Also, such issues do not alter the overall conclusion that the relationship between MAP and NBV remains intact in rats with ITED and reductions in NBF do not always precede diabetes-induced nerve dysfunction.…”

“…The levels of hyperglycaemia and insulinaemia appear to be important modulators of the blood pressure response to STZ, as insulin treatment has been documented to augment blood pressure in rats with experimental diabetes. 35,36 In this study, insulin treatment prevented severe hyperglycaemia and likely altered the severity and pathophysiology of disease.…”

Effects of angiotensin II on insulin receptor binding and mRNA levels in normal and diabetic rats

“…Other studies have investigated the blood pressure effect of insulin-dependent diabetes by use of the STZ-diabetic rat model and the results of these studies are conflicting inasmuch as increased [44][45][46], unchanged [47,48], and even decreased [49] levels have been reported in diabetics as compared to controls. Although technical problems related to the tailcuff method have been proposed as a possible explanation [44], these discrepancies are independent of the method of measurement of blood pressure and appear to be most likely related to differences in the age of rats, severity and duration of diabetes, presence of overt diabetic nephropathy, or dietary salt content.…”

Blood Pressure Characteristics of Female Spontaneously Diabetic Torii-Leprfa Rats

“…In STZ rats, the elevated blood pressure was reduced by doses of insulin. Therefore, poor glycemic control is considered to induce hypertension in diabetes mellitus [2,8]. Also, in ZDF rats, insulin reduced the blood pressure [13].…”