Van Buren T, Kasbergen C M, Gispen W H, De Wildt D J
Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Medical Faculty, Utrecht University, Netherlands.
Eur J Pharmacol. 1996 Feb 5;296(3):277-83. doi: 10.1016/0014-2999(95)00718-0.
Reduced nerve blood flow is thought to play an important role in the pathogenesis of diabetic neuropathy. This disturbance in nerve blood flow might be the consequence of either microangiopathy or an impaired autonomic innervation of the vasa nervorum. In order to differentiate between a vascular or an adrenergic-autonomic defect as the underlying cause of the disturbed nerve blood flow, we investigated the effects of the adrenocorticotropic hormone [ACTH]-(4-9) analogue Org 2766 on sciatic nerve blood flow under basal and adrenergic-stimulated conditions. Org 2766 has neuroprotective effects without cardiovascular effects. Treatment with Org 2766 was started 6 weeks after the induction of experimental diabetes mellitus. At week 12 the sciatic nerve blood flow, measured by laser-Doppler flowmetry, was reduced to 60% of the non-diabetic level; blood pressure was unchanged in diabetic rats compared to non-diabetic rats. Basal haemodynamic values were not affected by Org 2766 treatment. Vasa nervorum adrenergic responsiveness to tyramine (presynaptic) and phenylephrine (postsynaptic) was investigated. Diabetic rats showed adrenergic hyporesponsiveness. Treatment with Org 2766 restored the reduced presynaptic response to tyramine without affecting the reduced postsynaptic response to phenylephrine. It is concluded that a presynaptic-sympathetic deficit of nervi vasorum causes a disturbed flow responsiveness in diabetic rat sciatic nerve and that adrenergic autonomic disturbances in the vasa nervorum have only a small role in the reduced basal nerve blood flow of diabetic rats.
神经血流减少被认为在糖尿病性神经病变的发病机制中起重要作用。这种神经血流紊乱可能是微血管病变或神经滋养血管自主神经支配受损的结果。为了区分血管缺陷还是肾上腺素能自主神经缺陷是神经血流紊乱的潜在原因，我们研究了促肾上腺皮质激素[ACTH]-(4-9)类似物Org 2766在基础和肾上腺素能刺激条件下对坐骨神经血流的影响。Org 2766具有神经保护作用，而无心血管效应。在实验性糖尿病诱导6周后开始用Org 2766治疗。在第12周时，通过激光多普勒血流仪测量的坐骨神经血流降至非糖尿病水平的60%；与非糖尿病大鼠相比，糖尿病大鼠的血压没有变化。基础血流动力学值不受Org 2766治疗的影响。研究了神经滋养血管对酪胺（突触前）和去氧肾上腺素（突触后）的肾上腺素能反应性。糖尿病大鼠表现出肾上腺素能反应性降低。用Org 2766治疗可恢复对酪胺降低的突触前反应，而不影响对去氧肾上腺素降低的突触后反应。结论是，神经滋养血管的突触前交感神经缺陷导致糖尿病大鼠坐骨神经血流反应性紊乱，并且神经滋养血管中的肾上腺素能自主神经紊乱在糖尿病大鼠基础神经血流减少中仅起很小的作用。
