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Deficient nitric oxide responsible for reduced nerve blood flow in diabetic rats: effects of L‐NAME, L‐arginine, sodium nitroprusside and evening primrose oil
Author(s) -
Omawari Nagashige,
Dewhurst Mark,
Vo Phuong,
Mahmood Salina,
Stevens Elizabeth,
Tomlinson David R.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15384.x
Subject(s) - nitric oxide , endocrinology , medicine , sodium nitroprusside , nitroarginine , chemistry , sciatic nerve , anesthesia , nitric oxide synthase
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.