Long‐term angiotensin converting enzyme inhibition dose‐dependently improves nerve conduction velocity and evoked potential latencies in streptozotocin‐diabetic rats

Vascular disease probably plays an important role in the pathogenesis of cerebral complications that are associated with diabetes mellitus. Previous studies showed that treatment with the angiotensin converting enzyme-inhibitor enalapril (24 mg/kg) prevented neurophysiological and cognitive deficits in streptozotocin diabetic rats, and improved cerebral blood flow, despite a reduction in systemic mean arterial blood pressure. The present study examined if these effects could be sustained with long-term treatment, and if treatment with a lower dose (12 mg/kg) could prevent peripheral and central neurophysiological deficits without causing hypotension. Sciatic nerve conduction velocities were measured every three weeks after diabetes induction, until 24 weeks. Brain stem auditory (BAEP) and visual evoked potentials (VEP) were measured every three weeks from 10 weeks after diabetes induction, until 25 weeks. Nerve conduction velocity was decreased, and BAEP and VEP latencies increased in untreated diabetic rats. At the end of follow-up 12 mg/kg enalapril partially prevented evoked potential abnormalities, but not nerve conduction deficits, whereas 24 mg/kg enalapril largely prevented deficits in nerve conduction velocity (p<0.001), as well as BAEP (p<01) and VEP latencies (p<0.05). Mean arterial blood pressure was 122 mmHg in the untreated diabetic group, 75 mmHg in the 24 mg/kg group and 112 mmHg in the 12 mg/kg group. Sustained treatment with enalapril at 24 mg/kg was associated with increased mortality, which may be related to the marked hypotension at this dosage. We conclude that long-term treatment with enalapril at a dose of 24 mg/kg can prevent peripheral and central neurophysiological deficits in streptozotocin diabetic rats, but that adverse effects preclude sustained treatment.