Correction of neurovascular deficits in diabetic rats by β2-adrenoceptor agonist and α1-adrenoceptor antagonist treatment:: Interactions with the nitric oxide system

The aims were to test whether 2 weeks treatment with the beta(2)-adrenoceptor agonist, salbutamol, or the alpha(1)-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, N-G-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 alpha(1)-adrenoceptor blockade and beta(2)-adrenoceptor stimulation on nerve blood flow and conduction velocity were almost completely (76.7-91.7%) attenuated by N-G-nitro-L-arginine co-treatment. Thus, the data stress the importance of vasa nervorum alpha(1) and beta(2) adrenoceptors and the permissive role of nitric oxide in nerve blood flow control mechanisms. They also indicate that beta(2)-adrenoceptor agonists may be suitable for clinical trials of diabetic neuropathy. (C) 1998 Elsevier Science B.V.