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 prod uction and response in the development of endoneurial ischaemia in exp erimental diabetes. Rats were anaesthetized (Na pentobarbitone 45 mg k g(-1), diazepam 2 mg kg(-1)) for measurement of sciatic nerve laser Do ppler flux and systemic arterial pressure. Drugs were administered int o the sciatic endoneurium via a microinjector attached to a glass micr opipette. 2 In two separate studies comparing diabetic rats (streptozo tocin-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.) i n arbitrary units) was about half that measured in controls (219.6+/-5 2.4 and 212.8+/-95.5 respectively; P<0.005 for both). There were no si gnificant differences between the two in systemic arterial pressure. 3 Inhibition of nitric oxide production by microinjection of 1 nmol L-N AME into the endoneurium halved flux in controls (to 126.3+/-41.3 in S tudy 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 Dop pler flux. 4 L-Arginine (100 nmol), injected after L-NAME, markedly in creased 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 [7 5.8% (P<0.001) and 60.2% (P<0.02)]. The nitro-donor, sodium nitropruss ide (SNP; 10 nmol) had similar effects to L-arginine in both groups (i ncreases 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-arginin e 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.