Presynaptic deficit of sympathetic nerves: a cause for disturbed sciatic nerve blood flow responsiveness in diabetic rats.
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.
Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Medical Faculty, Utrecht University, Netherlands.
T
T
Van Buren
C M
CM
Kasbergen
W H
WH
Gispen
D J
DJ
De Wildt
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000098:blood supply*; D013311:Streptozocin; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014650:Vasa Nervorum / Q000294:innervation
D010446:Peptide Fragments; C013765:Org 2766; D013311:Streptozocin; D000324:Adrenocorticotropic Hormone