Impaired sensory-motor nerve function in the isolated mesenteric arterial bed of streptozotocin-diabetic and ganglioside-treated streptozotocin-diabetic rats.
1. Adult male Wistar rats were treated with streptozotocin (65 mg kg-1, i.p.) to induce diabetes. Subgroups of age-matched control and streptozotocin-treated rats were given daily injections of mixed brain bovine gangliosides (60 mg kg-1 body weight, i.p.). At eight weeks after treatment mesenteric arterial beds from rats in each of the four groups were isolated and perfused and the function of perivascular nerves (sympathetic and sensory-motor), endothelium and smooth muscle was assessed. 2. Values for basal tone of mesenteric beds from diabetic and diabetic-ganglioside rats were significantly lower than those of the control and control-ganglioside-treated rats. Perfusion pressures at basal tone were 25.55 +/- 0.8 (n = 11), 22.58 +/- 1.5 (n = 12), 28.42 +/- 1.6 (n = 12) and 30.67 +/- 1.9 (n = 12) mmHg for diabetic, diabetic-ganglioside, control and control-ganglioside-treated rats respectively. 3. There was no difference between the groups with respect to vasoconstrictor responses to sympathetic nerve stimulation, or to doses of noradrenaline. Vasoconstrictor responses to potassium chloride were also similar between the groups. 4. Perivascular nerve stimulation in the presence of the sympathetic blocker guanethidine (3 microM), with tone of the preparation raised with methoxamine (3-100 microM), elicited frequency-dependent vasodilatation of mesenteric arterial beds due to transmitter release from sensory-motor nerves. Sensory-motor nerve-induced vasodilator responses of mesenteric arterial beds from streptozotocin-diabetic and ganglioside-treated diabetic rats were significantly smaller than those of mesenteric beds from the controls (untreated and ganglioside-treated). Vasodilator responses to exogenously applied calcitonin gene-related peptide, the principal vasodilator transmitter released from these nerves, were not different between the groups. Vasodilator responses to the sensory neurotoxin capsaicin were also not different between the groups.5. Endothelium-dependent vasodilator responses to acetylcholine were similar between the groups as were those to the endothelium-independent vasodilator sodium nitroprusside.6. These results indicate that streptozotocin-induced diabetes produces marked impairment of sensory motor nerve function in the rat mesenteric arterial bed. The significantly lower basal perfusion pressures of mesenteric beds from diabetic rats compared to controls may be a reflection of sympathetic dysfunction, but no differences were apparent from the vasoconstrictor responses produced when sympathetic nerves were electrically stimulated. There was no evidence for changes in endothelial vasodilator function, or smooth muscle vasodilator and vasoconstrictor function. Ganglioside treatment did not modify any aspect of vascular function of mesenteric beds from streptozotocin-diabetic or control rats.
Ralevic
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V
Department of Anatomy and Developmental Biology, University College London.
Belai
A
A
Burnstock
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005732:Gangliosides / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000294:innervation* / Q000503:physiopathology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010525:Peripheral Nerves / Q000187:drug effects* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D005732:Gangliosides; D009599:Nitroprusside; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D002211:Capsaicin; D009638:Norepinephrine