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.
Cotter
M A
MA
Department of Biomedical Sciences, Marischal College, University of Aberdeen, Scotland, UK.
Cameron
N E
NE
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D017292:Doxazosin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D013311:Streptozocin; D019001:Nitric Oxide Synthase; D017292:Doxazosin; D000420:Albuterol