Adrenergic nerve function and contractile activity of the caudal artery of the streptozotocin diabetic rat

Hart, Jayne L.; Freas, William; McKenzie, Jack E.; Muldoon, Sheila M.

doi:10.1016/0165-1838(88)90007-0

Cited by 20 publications

(18 citation statements)

References 17 publications

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“…Previous reports have shown the reduction of NE content and stimulated overflow of endogenous NE in caudal arteries from STZ-induced diabetic rats, which reflects reduced innervation density of adrenergic nerves and/or inability to store NE. 19) It seems that this may be responsible for the reduction of not only NE synthesis but also reuptake of NE, suggesting dysfunction of prejunctional neurotransmitter regulatory mechanisms in GK rats. The extracellular concentration of the transmitter NE, which is the primary transmitter released from sympathetic post-ganglionic nerve terminals, depends dynamically on the rate of its release and clearance.…”

Section: Discussionmentioning

confidence: 99%

Dysfunction of Neurotransmitter Modulation System on Adrenergic Nerves of Caudal Artery in Type 2 Diabetic Goto–Kakizaki Rats

Ishii-Nozawa

Mita

Miyake

et al. 2012

Biological & Pharmaceutical Bulletin

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The Goto-Kakizaki (GK) rat is a non-obese and spontaneous model of mild Type 2 diabetes mellitus. In the present study, we compared the regulatory mechanisms of endogenous norepinephrine (NE) release from sympathetic nerves of caudal arteries of 12-week-old GK rats and age-matched normal Wistar rats. Electrical stimulation (ES) evoked significant NE release from caudal arteries of Wistar and GK rats. The amounts of NE released by ES were almost equal in Wistar and GK rats, although the NE content in caudal artery of GK rats was significantly lower than that of Wistar rats. We examined the effects of an α 2 -adrenoceptor agonist, clonidine (CLO), and an α 2 -adrenoceptor antagonist, yohimbine (YOH), on the release of endogenous NE evoked by ES. CLO significantly reduced NE release from caudal arteries of Wistar but not GK rats. On the other hand, YOH significantly increased NE release from both rats. Furthermore, we examined the effects of an A 1 -adenosine receptor agonist, 2-chloroadenosine (2CA), and an A 1 -adenosine receptor antagonist, 8-sulfophenyltheophylline (8SPT), on the release of endogenous NE evoked by ES. 2CA significantly reduced NE release from caudal arteries of Wistar but not GK rats. On the other hand, 8SPT did not affect NE release from both rats. These results suggest that the dysfunction of negative feedback regulation of NE release via presynaptic receptors on sympathetic nerves in GK rats may be involved in the autonomic nervous system dysfunction associated with diabetic autonomic neuropathy.Key words adrenergic nerve; diabetes mellitus; autonomic neuropathy; norepinephrine release; presynaptic receptor; rat caudal artery Neuropathies of the central and peripheral nervous systems are known to be caused by hyperglycemia, a consequence of the deregulation of glucose in diabetes. Diabetic neuropathy is a painful complication involving progressive neuronal damage and dysfunction. Some reports indicate the appearance of peripheral neuropathy in a diabetic animal model, which affects the sensory nerves, 1) the autonomic nervous system 2,3) and even the central nervous system. 4) Autonomic dysfunction is a particularly significant complication of diabetes that may be responsible for orthostatic hypotension, skin ulceration, arterial calcification and abnormal temperature regulation. 5)However, most animal models of diabetic neuropathy are Type 1 diabetic models, namely, streptozotocin (STZ)-induced diabetic rats and mice. 6)Goto-Kakizaki (GK) rats were established as a model of inbred type 2 diabetes mellitus by selective breeding from originally non-diabetic Wistar rats using glucose intolerance. 7) GK rats have been shown to develop Type 2 diabetes without obesity spontaneously and to exhibit higher post-prandial plasma glucose levels and lower post-prandial immunoreactive insulin levels than Wistar rats. 8,9) GK rats are particularly relevant to human Type 2 diabetes because the pathogenesis of GK rats includes peripheral insulin resistance, hyperinsulinemia, hyperglycemia and glucose intole...

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Section: Discussionmentioning

confidence: 99%

Dysfunction of Neurotransmitter Modulation System on Adrenergic Nerves of Caudal Artery in Type 2 Diabetic Goto–Kakizaki Rats

Ishii-Nozawa

Mita

Miyake

et al. 2012

Biological & Pharmaceutical Bulletin

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“…The pathogenesis of diabetic neuropathy has been extensively studied in the streptozotocin-treated rat, a model of insulin-dependent diabetes. In this model, sympathetic dysfunction is suggested by attenuated contractile responses due to stimulation of sympathetic nerves in the rat mesenteric bed (Takiguchi et al, 1988) and tail artery (Hart et al, 1988). Ultrastructural changes in sympathetic ganglia (Monckton & Pehowich, 1982) and neuronal deficits in tyrosine hydroxylase (the ratelimiting enzyme in the synthesis of noradrenaline) and 5-hydroxytryptamine (5-HT) specific to mesenteric perivascular sympathetic nerves (Webster et al, 1991) have also been seen.…”

Section: Introductionmentioning

confidence: 97%

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

Ralevic

Belai

Burnstock

1993

British J Pharmacology

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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.

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“…Most of these studies have used the streptozotocin (STZ)-treated rat model of type 1 diabetes and have investigated effects in the rat tail artery, a cutaneous thermoregulatory vessel with a function similar to that of digital arteries in man, and mesenteric arteries (MA). 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).…”

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confidence: 99%

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

Johansen

Tripovic

Brock

2013

American Journal of Physiology-Heart and Circulatory Physiology

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Johansen NJ, Tripovic D, Brock JA. Streptozotocin-induced diabetes differentially affects sympathetic innervation and control of plantar metatarsal and mesenteric arteries in the rat. Am J Physiol Heart Circ Physiol 304: H215-H228, 2013. First published November 16, 2012; doi:10.1152/ajpheart.00661.2012.-In humans neural control of arterial vessels supplying skin in the extremities is particularly vulnerable to the effects of diabetes. Here the streptozotocin (STZ) rat model of type 1 diabetes was used to compare effects on neurovascular function in plantar metatarsal arteries (PMAs), which supply blood to skin of hind paw digits, with those in mesenteric arteries (MAs). Twelve weeks after STZ (60 mg/kg ip), wire myography was used to assess vascular function. In PMAs, lumen dimensions were unchanged but both nerve-evoked contractions and sensitivity to ␣1 (phenylephrine, methoxamine)-and ␣2 (clonidine)-adrenoceptor agonists were reduced. The density of perivascular nerve fibers was also reduced by ϳ25%. These changes were not observed in PMAs from STZ-treated rats receiving either a low dose of insulin that did not greatly reduce blood glucose levels or a high dose of insulin that markedly reduced blood glucose levels. In MAs from STZ-treated rats, nerve-evoked increases in force did not differ from control but, because lumen dimensions were ϳ20% larger, nerveevoked increases in effective transmural pressure were smaller. Increases in effective transmural pressure produced by phenylephrine or ␣,␤-methylene ATP in MAs from STZ-treated rats were not smaller than control, but the density of perivascular nerve fibers was reduced by ϳ10%. In MAs, the increase in vascular dimensions is primarily responsible for reducing effectiveness of nerve-evoked constrictions. By contrast, in PMAs decreases in both the density of perivascular nerve fibers and the reactivity of the vascular muscle appear to explain impairment of neurovascular transmission. diabetes; sympathetic innervation; neurovascular transmission IN HUMANS ABNORMAL CONTROL of the vasculature has been implicated in the etiology of many diabetes-related complications such as neuropathy and diabetic foot ulceration (41). These changes involve endothelium-dysfunction (30) as well as deficits in both sympathetic nerve-mediated vasoconstriction (see below) and sensory nerve-mediated vasodilation (1). However, the mechanisms whereby diabetes affects sympathetic and sensory nerve regulation of the vasculature are not well understood, although it is believed that diabetes causes degeneration of these nerve supplies (34).Many clinical studies have evaluated the effects of diabetes on sympathetic nerve-mediated vasoconstriction of arterial vessels supplying plantar skin of the foot. These studies have demonstrated that both type 1 (insulin dependent) and type 2 (noninsulin dependent) diabetic patients with signs of sensory and/or autonomic neuropathy (e.g., orthostatic hypertension) have increased skin blood flow under basal conditions (2, 33) and attenuated reductions i...

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Adrenergic nerve function and contractile activity of the caudal artery of the streptozotocin diabetic rat

Cited by 20 publications

References 17 publications

Dysfunction of Neurotransmitter Modulation System on Adrenergic Nerves of Caudal Artery in Type 2 Diabetic Goto–Kakizaki Rats

Dysfunction of Neurotransmitter Modulation System on Adrenergic Nerves of Caudal Artery in Type 2 Diabetic Goto–Kakizaki Rats

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

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

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