Effect of diabetes on relaxations to non-adrenergic, non-cholinergic nerve stimulation in longitudinal muscle of the rat gastric fundus.

1. The effect of 8-week streptozotocin-induced diabetes has been examined on relaxations to non-adrenergic, non-cholinergic (NANC) nerve stimulation in longitudinal strips of rat gastric fundus. 2. In the presence of noradrenergic and cholinergic blockade and raised tissue tone, electrical field stimulation (0.5-4 Hz, 30 s trains) induced frequency-dependent relaxations that were significantly smaller in gastric fundus strips from diabetic rats than in strips from control rats. 3. NG-nitro-L-arginine methyl ester (NAME, 100 microM) significantly reduced NANC relaxations in muscle strips from both control and diabetic rats, but the reduction was greater in muscle strips from diabetic rats than in those from control rats at frequencies of 2 and 4 Hz. alpha-Chymotrypsin (1 u ml-1) slightly reduced relaxations to nerve stimulation in muscle strips from both control and diabetic rats. 4. The duration of NANC nerve relaxations (1-4 Hz, 30 s trains) was smaller in muscle strips from diabetic rats than in those from control rats. The duration of NANC relaxations was reduced by alpha-chymotrypsin (1 u ml-1) in muscle strips from control rats but not in muscle strips from diabetic rats. 5. Relaxations to both nitric oxide (NO; 1-30 microM) and vasoactive intestinal polypeptide (VIP; 0.1-30 microM) were concentration-dependent and did not differ between muscle strips from control and diabetic rats. 6. The results suggest that streptozotocin-induced diabetes impairs relaxations to NANC nerve stimulation in the rat gastric fundus, which are largely mediated by NO and to a lesser extent by VIP. The impairment appears to occur at the prejunctional level, as smooth muscle reactivity to NO and VIP is not altered.