The effects of concurrent hypertension on the development of peripheral neuropathy in STZ‐diabetic rats

The most widely used animal model to study peripheral diabetic neuropathy is the streptozotocin (STZ)‐diabetic rat. A limitation of this model is that STZ‐diabetic rodents do not develop hypertension, which is a risk factor for neuropathy in diabetic subjects. We have investigated the hypothesis that combining hypertension with STZ‐diabetes in the rat will exaggerate peripheral neuropathy and more accurately reflect the human condition. Experiments were performed using spontaneously hypertensive rats (SHR) and WKY rats as normotensive controls. A subgroup of each strain was made diabetic by STZ injection and rats were maintained for a further 24 weeks prior to assessing nerve function. Compared to WKY animals, SHR rats had significantly higher blood pressure (BP) (p<0.01). STZ‐diabetes led to a reduction in BP in both WKY and SHR rats (p<0.01). Motor and sensory nerve conduction velocity was significantly lower in both diabetic WKY and SHR rats compared to strain matched controls (P<0.001) and in the SHR diabetic rats this decrease was exaggerated (P<0.05 vs WKY diabetic rats). SHR rats displayed a reduction in nerve blood flow compared to WKY rats regardless of diabetes (p<0.01). These studies suggest that hypertension exaggerates diabetes‐induced neuropathy. Rats with hyperglycemia and hypertension may provide a suitable model for studying the etiology of diabetic neuropathy.