Impaired sensory‐motor nerve function in the isolated mesenteric arterial bed of streptozotocin‐diabetic and ganglioside‐treated streptozotocin‐diabetic rats

Abstract

1 Adult male Wistar rats were treated with streptozotocin (65 mg kg-', 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' 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 tM), with tone of the preparation raised with methoxamine (3-100 IM), 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 sensorymotor 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.

Streptozotocin-induced diabetes differentially affects sympathetic innervation and control of plantar metatarsal and mesenteric arteries in the rat

“…Sensory nerve-mediated vasodilation of the perfused isolated mesenteric arterial bed has been reported to be reduced in rats 8 wk after induction of diabetes with STZ (28). However, in the present study, we observed no changes in the peptidergic innervation of either MAs or PMAs.…”

“…In tail artery, Hart et al (11) reported that 8 wk of diabetes produced a small reduction in sympathetic nerve-mediated vasoconstriction, whereas Weber and MacLeod (42) and Speirs et al (32) reported that 12 wk of diabetes did not reduce sympathetic nerve-mediated vasoconstriction. In the perfused mesenteric arterial bed, diabetes reduced sympathetic nerve-mediated pressor responses after 12 wk of diabetes (27), but this effect was not present after 8 wk (28). In mesenteric arteries, it is not known if the decrease in the sympathetic nerve-mediated pressor response produced by diabetes is associated with degeneration of the sympathetic nerve supply, but in tail artery the perivascular sympathetic innervation is not affected by 12 wk of diabetes (32).…”

Mesenteric arterial function in the rat in pregnancy: role of sympathetic and sensory‐motor perivascular nerves, endothelium, smooth muscle, nitric oxide and prostaglandins

“…Virgin females and 21-day pregnant rats (term, 22 days) were killed by carbon dioxide asphyxiation. Mesenteric arterial beds were isolated and set up for perfusion by the method of McGregor (1966) essentially as described previously (Ralevic et al, 1993). The abdomen was opened and the superior mesenteric artery exposed and cannulated with a hypodermic needle.…”

Effects of chronic vitamin E deficiency and a high polyunsaturated fatty acid diet on rat mesenteric arterial function

“…Mesenteric beds were isolated from the rats and set up for perfusion as described previously (Ralevic et al, 1993). The abdomen was opened and the superior mesenteric artery exposed and cannulated with a hypodermic needle.…”