Effect of aminoguanidine on the impaired nitric oxide-mediated neurotransmission in anococcygeus muscle from diabetic rats.
The contribution of advanced glycation end-product (AGE) formation to alterations in nitrergic neurotransmission caused by 8-week streptozotocin-induced diabetes has been examined in the rat anococcygeus muscle. Relaxant responses to nitrergic nerve stimulation (0.5-5 Hz, 10-sec train), to nitric oxide (NO; 0.1-3 microM), to the NO donor, sodium nitroprusside (SNP; 5-500 nM), and to the cell-permeable analogue of cyclic guanosine monophosphate (cGMP), 8-bromo-cGMP (15 and 30 microM), were significantly smaller in muscles from diabetic rats than from control rats. Pretreatment with aminoguanidine hemisulphate (1 milligram drinking water) to inhibit AGE formation, did not alter the relaxant responses to nitrergic nerve stimulation, NO or SNP in tissues from control rats, or responses to NO or SNP in tissues from diabetic rats, however relaxations to nitrergic nerve stimulation were further reduced in tissues from diabetic rats. In anococcygeus muscles from untreated animals, a 20-min exposure to aminoguanidine (1 mM) in vitro had no effect on relaxations to nitrergic nerve stimulation. The results suggest that diabetes impairs nitrergic transmission in the rat anococcygeus at least partly through alterations in the cGMP-relaxation pathway. The impaired neurotransmission does not appear to be related to the formation of AGEs.
Way
K J
KJ
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Reid
J J
JJ
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
D001786:Blood Glucose; D006146:Guanidines; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; C004479:pimagedine