Skip to main content
SpringerLink
Log in

Effects of evening primrose oil treatment on sciatic nerve blood flow and endoneurial oxygen tension in streptozotocin-diabetic rats

  • Originals
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

Evening primrose oil (EPO) is rich in the Ω-6 essential fatty acid component, γ-linolenic acid. The aim of the investigation was to determine whether EPO treatment prevented a reduction in sciatic nerve perfusion and oxygenation in streptozotocin-diabetic rats. Rats were treated from diabetes induction with 10 g EPO kg−1 day−1. Sciatic blood flow was measured by microelectrode polarography and hydrogen clearance. Diabetes caused 47.7%±3.4% (P<0.001) and 58.8%±4.8% (P<0.001) reduction in the nutritive (capillary) and the non-nutritive (large vessel) components of endoneurial blood flow, respectively, which were prevented by EPO. Treatment had no significant effect on nutritive flow in non-diabetic rats; however, the rate of non-nutritive flow increased by 97.7%±38.9% (P<0.01). Sciatic endoneurial oxygen tension was measured by microelectrode polarography. Diabetes resulted in a 44.7%±3.4% reduction in mean oxygen tension (P<0.001), which was largely (82.3%±10.2%) prevented by EPO treatment (P<0.001). Thus, EPO prevents impairment of blood flow and endoneurial oxygenation in experimental diabetes. It is likely that this neurovascular action accounts for the beneficial effects of treatment on nerve function in diabetic rats and patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gregerson G, Diabetic neuropathy: influence of age, sex, metabolic control and duration of diabetes on motor conduction velocity. Neurology 17:972–980, 1967

    Google Scholar 

  2. Gregersen G, A study of peripheral nerves in diabetic subjects during ischaemia. J Neurol Neurosurg Psychiatry 31:175–181, 1968

    Google Scholar 

  3. Eliasson SG, Nerve conduction changes in experimental diabetes. J Clin Invest 43:2352–2358, 1964

    Google Scholar 

  4. Seneviratne KN, Peiris OA, The effects of hypoxia on the excitability of isolated peripheral nerves of alloxan-diabetic rats. J Neurol Neurosurg Psychiatry 32:462–469, 1969

    Google Scholar 

  5. Greene DA, Lattimer SA, Sima AAF, Pathogenesis and prevention of diabetic neuropathy. Diab Metab Rev 4:201–221, 1988

    Google Scholar 

  6. Low PA, Tuck RR, Takeuchi M, Nerve microenvironment in diabetic neuropathy. In: Dyck PJ, Thomas PK, Asbury AK, Winegrad AI, Porte D (eds) Diabetic neuropathy. Saunders, Philadelphia, pp 266–278, 1987

    Google Scholar 

  7. Cameron NE, Cotter MA, Low PA, Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits. Am J Physiol 261:E1-E8, 1991

    Google Scholar 

  8. Cameron NE, Cotter MA, Potential therapeutic approaches to the treatment or prevention of diabetic neuropathy: evidence from experimental studies. Diabetic Med 10:593–605, 1993

    Google Scholar 

  9. Newrick PG, Wilson AJ, Jakubowski J, Boulton AJM, Ward JD, Sural nerve oxygen tension in diabetes. BMJ 293:1053–1054, 1986

    Google Scholar 

  10. Tesfaye S, Harris N, Jakubowski JJ, Mody C, Wilson RM, Rennie IG, Ward JD, Impaired blood flow and arterio-venous shunting in human diabetic neuropathy: a novel technique of nerve photography and fluorescein angiography. Diabetologia 36: 1266–1274, 1993

    Google Scholar 

  11. Julu POO, Essential fatty acids prevent slowed nerve conduction velocity in streptozotocin diabetic rats. J Diab Comp 2: 185–188, 1988

    Google Scholar 

  12. Tomlinson DR, Robinson JP, Compton AM, Essential fatty acid treatment—effects on nerve conduction, polyol pathway and axonal transport in streptozotocin diabetic rats. Diabetologia 32:655–659, 1989

    Google Scholar 

  13. Cameron NE, Cotter MA, Robertson S, Effects of essential fatty acid dietary supplementation on peripheral nerve and skeletal muscle function and capillarisation in streptozotocin diabetic rats. Diabetes 40:532–539, 1991

    Google Scholar 

  14. Keen H, Payan J, Allawi J, Walker J, Jamal G, Weir A, Henderson L, Bissessar E, Watkins P, Sampson M, Gale E, Scarpello J, Boddie H, Hardy K, Thomas P, Misra P, Halonen J, Treatment of diabetic neuropathy with γ-linolenic acid. Diabetes Care 16:8–15, 1993

    Google Scholar 

  15. Horrobin DF, Manku MS, Clinical biochemistry of essential fatty acids. In: Horrobin DF (ed) Omega-6 essential fatty acids: pathophysiology and roles in clinical medicine. Liss, New York, pp 21–54, 1990

    Google Scholar 

  16. Julu POO, Mutamba A, Comparison of short-term effects of insulin and essential fatty acids on the slowed nerve conduction of streptozotocin diabetes in rats. J Neurol Sci 106:56–59, 1991

    Google Scholar 

  17. Stevens EJ, Lockett MJ, Carrington AL, Tomlinson DR, Essential fatty acid treatment prevents nerve ischaemia and associated conduction anomalies in rats with experimental diabetes mellitus. Diabetologia 36:111–117, 1993

    Google Scholar 

  18. Cameron NE, Cotter MA, Dines KC, Robertson S, Cox D, The effects of evening primrose oil on peripheral nerve function and capillarization in streptozotocin-diabetic rats: modulation by the cyclo-oxygenase inhibitor flurbiprofen. Br J Pharmacol 109:972–979, 1993

    Google Scholar 

  19. Tuck RR, Schmelzer JD, Low PA, Endoneurial blood flow and oxygen tension in the sciatic nerves of rats with experimental diabetic neuropathy. Brain 107:935–950, 1984

    Google Scholar 

  20. Day TJ, Lagerlund TD, Low PA, Analysis of H2 clearance curves used to measure blood flow in rat sciatic nerve. J Physiol 414: 35–54, 1989

    Google Scholar 

  21. Low PA, Lagerlund TD, McManis PG, Nerve blood flow and oxygen delivery in normal, diabetic and ischemic neuropathy. Int Rev Neurobiol 31:355–438, 1989

    Google Scholar 

  22. Rundquist I, Smith QR, Michel ME, Ask P Öberg PÅ, Rapaport SI, Sciatic nerve blood flow measured by laser Doppler flowmetry and [14C]idoantipyrine. Am J Physiol 248:H311-H317, 1985

    Google Scholar 

  23. Scarphedisson JO, Hårding H, Thorén P, Repeated measurements of cerebral blood flow in rats. Comparisons between the hydrogen clearance method and laser Doppler flowmetry. Acta Physiol Scand 134:133–142, 1988

    Google Scholar 

  24. Cameron NE, Cotter MA, Ferguson K, Robertson S, Radcliffe MA, Effects of chronic α-adrenergic receptor blockade on peripheral nerve conduction, hypoxic resistance, polyols, Na-K ATPase activity and vascular supply in streptozotocin-diabetic rats. Diabetes 40:1652–1658, 1991

    Google Scholar 

  25. Cameron NE, Cotter MA, Robertson S, Angiotensin converting enzyme inhibition prevents the development of muscle and nerve dysfunction and stimulates angiogenesis in streptozotocin-diabetic rats. Diabetologia 35:12–18, 1992

    Google Scholar 

  26. Hudlická O, Tyler KR, Angiogenesis: the growth of the vascular system. Academic Press, New York, 1986

    Google Scholar 

  27. Cotter MA, Dines KC, Cameron NE, Comparison of the effects of evening primrose oil and the putative active triglyceride, dilinolein mono-γ-linolenate (DLMG), on sciatic nerve conduction velocity in diabetic rats: dose-response relationship and modulation of endoneurial blood flow. Diabetic Med 10 [Suppl 3]:P67, 1993

  28. Dines KC, Cotter MA, Cameron NE, Contrasting effects of treatment with ω-3 and ω-6 essential fatty acids on peripheral nerve function and capillarization in streptozotocin-diabetic rats. Diabetologia 36:1132–1138, 1993

    Google Scholar 

  29. Lands WEM, Biochemistry and physiology ofn-3 fatty acids. FASEB J 6:2530–2536, 1992

    Google Scholar 

  30. Cotter MA, Dines KC, Cameron NE, Prevention and reversal of motor and sensory peripheral nerve conduction abnormalities in streptoztocin-diabetic rats by the prostacyclin analogue iloprost. Naunyn-Schmiedeberg's Arch Pharmacol 347:534–540, 1993

    Google Scholar 

  31. Hotta N, Koh N, Sakakibara F, Nakamura J, Kakuta H, Fukasawa H, Sakamoto N, Effect of beraprost sodium, a prostaglandin I2 analogue on diabetic neuropathy of rats. Diabetes 42 [Suppl 1]:101A, 1993

  32. Ward KK, Low PA, Schmelzer JD, Zochodne DW, Prostacyclin and noradrenaline in peripheral nerve of chronic experimental diabetes in rats. Brain 112:197–208, 1989

    Google Scholar 

  33. Cameron NE, Cotter MA, Impaired contraction and relaxation in aorta from streptozotocin-diabetic rats: role of polyol pathway activity. Diabetologia 35:1011–1019, 1992

    Google Scholar 

  34. Tesfamariam B, Palacino JJ, Weisbrod RM, Cohen RA, Aldose reductase inhibition restores endothelial cell function in diabetic rabbit aorta. J Cardiovasc Pharmacol 21:205–211, 1993

    Google Scholar 

  35. Langenstroer P, Pieper GM, Regulation of spontaneous EDRF release in diabetic rat aorta by oxygen free radicals. Am J Physiol 263:H257-H265, 1992

    Google Scholar 

  36. Cameron NE, Cotter MA, Dines KC, Maxfield EK, Effects of aldose reductase inhibition on nerve blood flow and oxygen tension in diabetic rats. Diabetologia 36 [Suppl 1]:A199, 1993

  37. Cameron NE, Cotter MA, Archibald V, Dines KC, Maxfield EK, Anti-oxidant and pro-oxidant effects on nerve conduction velocity, endoneurial blood flow and oxygen tension in non-diabetic and streptozotocin-diabetic rats. Diabetologia 37:449–459, 1994

    Google Scholar 

  38. Maxfield EK, Cameron NE, Cotter MA, Dines KC, Angiotensin II receptor blockade improves nerve function, modulates nerve blood flow and stimulates endoneurial angiogenesis in streptozotocin-diabetic rats. Diabetologia 36:1230–1237, 1993

    Google Scholar 

  39. Takeda Y, Miyamori I, Yoneda T, Takeda R, Production of endothelin-1 from the mesenteric arteries of streptozotocin-induced diabetic rats. Life Sci 48:2553–2556, 1991

    Google Scholar 

  40. Derwahl M, Schmermund A, Hamacher C, Schifferdecker E, Schatz H, Expression of endothelin 1 in diabetics with peripheral vascular disease. Diabetologia 36 [Suppl 1]:A203, 1993

  41. Ceriello A, Coagulation activation in diabetes mellitus: the role of hyperglycaemia and therapeutic prospects. Diabetologia 36:1119–1125, 1993

    Google Scholar 

  42. Cameron NE, Cotter MA, Dines KC, Maxfield EK, Pharmacological manipulation of vascular endothelium in non-diabetic and streptozotocin-diabetic rats: effects on nerve conduction, hypoxic resistance and endoneurial capillarization. Diabetologia 36:516–522, 1993

    Google Scholar 

  43. Ditzel J, Andersen H, Peters ND, Increased haemoglobin A1c and 2,3-diphosphoglycerate in diabetes and their effects on redcell oxygen-releasing capacity. Lancet II:1034, 1973

    Google Scholar 

  44. Low PA, Schmelzer JD, Ward KK, Yao JK, Experimental chronic hypoxic neuropathy: relevance to diabetic neuropathy. Am J Physiol 250:E94-E99, 1986

    Google Scholar 

  45. Strupp M, Jund R, Schneider U, Grafe P, Glucose availability and sensitivity to anoxia of isolated rat peroneal nerve. Am J Physiol 261:E389-E394, 1991

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences, University of Aberdeen, Marischal College, AB9 1AS, Aberdeen, UK

    N. E. Cameron & M. A. Cotter

Authors
  1. N. E. Cameron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. A. Cotter
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cameron, N.E., Cotter, M.A. Effects of evening primrose oil treatment on sciatic nerve blood flow and endoneurial oxygen tension in streptozotocin-diabetic rats. Acta Diabetol 31, 220–225 (1994). https://doi.org/10.1007/BF00571955

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00571955

Key words

Search

Navigation