Correction of neurovascular deficits in diabetic rats by beta2-adrenoceptor agonist and alpha1-adrenoceptor antagonist treatment: interactions with the nitric oxide system.

The aims were to test whether 2 weeks treatment with the beta2-adrenoceptor agonist, salbutamol, or the alpha1-adrenoceptor antagonist, doxazosin, could correct nerve blood flow and conduction velocity deficits in 8 week streptozotocin-diabetic rats and to examine neurovascular mechanisms using co-treatment with the nitric oxide synthase inhibitor, NG-nitro-L-arginine. Sciatic motor conduction velocity, 20.3% reduced by diabetes, was corrected by 88.2 and 88.5% for salbutamol and doxazosin, respectively. A 47.6% diabetic deficit in sciatic nutritive endoneurial blood, was substantially reversed by salbutamol (117.0%) and doxazosin (61.0%) treatment. The effects of alpha1-adrenoceptor blockade and beta2-adrenoceptor stimulation on nerve blood flow and conduction velocity were almost completely (76.7-91.7%) attenuated by NG-nitro-L-arginine co-treatment. Thus, the data stress the importance of vasa nervorum alpha1 and beta2 adrenoceptors and the permissive role of nitric oxide in nerve blood flow control mechanisms. They also indicate that beta2-adrenoceptor agonists may be suitable for clinical trials of diabetic neuropathy.