European Journal of Biomedical and Pharmaceutical Sciences

UNCOUPLING OF NITRIC OXIDE SYNTHASE PREDISPOSES DIABETIC RATS TO CARDIOVASCULAR RISK EVENTS

Dallatu M. K.*, Anaja P. O., Agaie B. M. and Bunza J. M.

ABSTRACT

It has previously been established that diabetes is associated with endothelial dysfunction resulting from decrease in the activities of endothelial nitric oxide synthase (eNOS) leading to reduced nitric oxide (NO) production. In the current work, we hypothesized that acute hyperglycaemia alone may affect the vascular beds differently, leading to endothelial dysfunction and the loss of cardiovascular protection in diabetes. Adult male and female Sprague-Dawley rats, 9–11 weeks of age were divided into three groups: controls (5 males and 5 female), diabetics (5 males and 5 females) and diabetics supplemented with tetrahydrobiopterin, 20mg/kgbw/day for two weeks. Diabetic groups received a single i.v. injection of streptozotocin (STZ, 60 mg/ kg) while the control group were injected with a similar volume of citrate buffer. Results shows total cholesterol was 144.30±3.51 mg/dl, 145.66±3.78 mg/dl in controls, 165.30±3.84 mg/dl and 177.01±2.49 mg/dl in diabetics and 152.57±2.75 mg/dl, 157.70±2.02 mg/dl in diabetics supplemented respectively. HDLC was 34.40±0.42 mg/dl, 39.28±1.45 mg/dl in controls, 31.49±1.11 mg/dl, 26.59±3.12 mg/dl in diabetics and 35.05±0.73 mg/dl, 36.35±1.24 mg/dl in diabetic supplemented respectively. LDL-C was 91.87±3.48 mg/dl, 86.98±3.36 mg/dl in controls, 108.72±2.81, mg/dl 124.40±4.41 mg/dl diabetics, 94.31±3.38 mg/dl, 97.79±2.46 mg/dl diabetics supplemented respectively. VLDL-C was 18.08±1.10 mg/dl, 19.40±0.70 mg/dl in controls, 25.08±0.41 mg/dl, 26.00±0.82 mg/dl in diabetics, 23.04±0.83 mg/dl, 23.50±0.29 mg/dl in diabetics supplemented. TG was 123.50±5.39 mg/dl, 97.00±3.49 mg/dl in controls, 125.00±2.61 mg/dl, 130.00±4.08 mg/dl in diabetics, 115.20±4.13 mg/dl, 117.75±1.60 mg/dl diabetics supplemented. AIX was 4.21±0.14, 3.72±0.15 in controls, 5.26±0.13, 6.98±0.92 in diabetics, 4.36±0.10, 4.37±0.15 in diabetics supplemented respectively. With the exception of TG and VLDL-C, differences observed between controls, diabetics and diabetics supplemented were significant (P˂0.05). Treatment with tetrahydrobioptherin, a known cofactor of NOS, tend to reversed all the anomalies to near control values, hence we conclude, uncoupling of NOS by diabetes, may predispose these subjects to cardiovascular events that may be reversed by treatment with tetrahydrobiopterin.

Keywords: Diabetes mellitus, Lipid Profile, Cardiovascular events, Tetrahydrobiopterin.