A disturbed macrocirculatory supply as a determinant for a reduced sciatic nerve blood flow in diabetic rats.
The aim of this study was to evaluate macrocirculatory disturbances in relation to the reduced sciatic nerve blood flow seen in diabetic rats. Therefore, both femoral blood flow, the macrocirculatory arterial blood supply to the sciatic nerve, and the microcirculatory neuronal blood flow were measured. In order to differentiate between a direct vascular or a neuronal defect as a cause for the disturbed macrocirculatory blood flow the effects of the adrenocorticotropic hormone [ACTH]-(4-9) analogue, Org 2766, a neurotrophic compound without cardiovascular effects, were investigated on the femoral flow under basal as well as adrenergic-stimulated conditions. Adrenergic responsiveness to tyramine and phenylephrine effect on femoral flow was determined. Basal sciatic nerve and femoral blood flow were reduced by 48% and 42%, respectively, after 12 weeks of diabetes, without effect on blood pressure. Treatment with Org 2766, beginning 6 weeks after the induction of diabetes, had no influence on these basal haemodynamic variables. Femoral flow in diabetic rats showed a smaller response to tyramine and phenylephrine compared to the control. Org 2766 restored this disturbed flow response to that of the control rats. In conclusion, the decrease in basal femoral flow might be responsible for the lowered sciatic nerve blood flow. Although neuronal disturbances due to diabetes had a very minor role in the reduction of basal femoral blood flow the adrenergic-stimulated flow responsiveness was seriously affected in diabetic rats.
Van Buren
T
T
Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Medical Faculty, Utrecht University, Netherlands.
Kappelle
A C
AC
Kasbergen
C M
CM
Gispen
W H
WH
De Wildt
D J
DJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000098:blood supply*; D014439:Tyramine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D010446:Peptide Fragments; D010656:Phenylephrine; C013765:Org 2766; D000324:Adrenocorticotropic Hormone; D014439:Tyramine