Deficient nitric oxide responsible for reduced nerve blood flow in diabetic rats: Effects of L-NAME, L-arginine, sodium nitroprusside and evening primrose oil

1 This study examined the potential role of impaired nitric oxide production and response in the development of endoneurial ischaemia in experimental diabetes. Rats were anaesthetized (Na pentobarbitone 45 mg kg(-1), diazepam 2 mg kg(-1)) for measurement of sciatic nerve laser Doppler flux and systemic arterial pressure. Drugs were administered into the sciatic endoneurium via a microinjector attached to a glass micropipette. 2 In two separate studies comparing diabetic rats (streptozotocin-induced; 8-10 wk duration) with controls, nerve Doppler flux in diabetic rats (Study 1, 116.6+/-40.4 and Study 2, 90.1+/-34.7 (s.d.) in arbitrary units) was about half that measured in controls (219.6+/-52.4 and 212.8+/-95.5 respectively; P<0.005 for both). There were no significant differences between the two in systemic arterial pressure. 3 Inhibition of nitric oxide production by microinjection of 1 nmol L-NAME into the endoneurium halved flux in controls (to 126.3+/-41.3 in Study 1 and 102.1+/-38.9 in Study 2; both P<0.001), with no significant effect in diabetic rats, indicating markedly diminished tonic nitric oxide production in the latter. D-NAME was without effect on nerve Doppler flux. 4 L-Arginine (100 nmol), injected after L-NAME, markedly increased flux in controls (by 65.8% (P<0.03) and 97.8% (P<0.01) in the two studies) and by proportionally similar amounts in diabetic rats [75.8% (P<0.001) and 60.2% (P<0.02)]. The nitro-donor, sodium nitroprusside (SNP; 10 nmol) had similar effects to L-arginine in both groups (increases of 66.0% in controls and 77.5% in diabetics; both P<0.002). 5 A second diabetic group, treated with evening primrose oil performed exactly like control rats in respect of responses to L-NAME, L-arginine and SNP. 6 These findings implicate deficient nitric oxide in nerve ischaemia of diabetes and suggest correction thereof as a mechanism of action of evening primrose oil.