Looking to the future: diabetic neuropathy and effects of rosuvastatin on neurovascular function in diabetes models.
Vascular defects contribute substantially to neuropathic changes associated with metabolic abnormalities in diabetes. Statins appear to exert beneficial effects on vascular function independent of cholesterol lowering. In studies of the streptozotocin-induced diabetes rat model, rosuvastatin treatment was shown to correct sciatic motor and saphenous sensory nerve conduction velocity deficits (large fiber defects), thermal hyperalgesia (small fiber defects) and deficits in sciatic nerve and superior cervical ganglion blood flow. Rosuvastatin reversed deficits in nitrergic nerve-mediated vasodilation in the corpus cavernosum and corrected deficits in endothelium-derived hyperpolarising factor-mediated vasodilation in mesenteric vessels. Rosuvastatin did not alter plasma cholesterol in diabetic animals (a characteristic effect in this model), but significantly lowered triglycerides at high doses. Treatment with mevalonate reversed the beneficial effects of rosuvastatin on nerve function and blood flow, suggesting that the effects are mediated by inhibition of the cholesterol biosynthesis pathway in the absence of cholesterol reduction. Thus, rosuvastatin has wide-ranging neurovascular actions in diabetic rats that may be independent of lipid-lowering activity.
Cameron
Norman
N
Department of Biomedical Science, Institute of Medical Science, Aberdeen University, Aberdeen AB9 1AS, UK. n.e.cameron@abdn.ac.uk
Cotter
Mary
M
Inkster
Melanie
M
Nangle
Matthew
M
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005464:Fluorobenzenes / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D009431:Neural Conduction / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D000068718:Rosuvastatin Calcium; D012584:Sciatic Nerve / Q000098:blood supply; D013449:Sulfonamides / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium