Endothelial function in the isolated perfused mesentery and aortae of rats with streptozotocin‐induced diabetes: effect of treatment with the aldose reductase inhibitor, ponalrestat

Taylor, Paul D.; Wickenden, Alan D.; Mirrlees, Donald J.; Poston, Lucilla

doi:10.1111/j.1476-5381.1994.tb14021.x

Cited by 64 publications

(40 citation statements)

References 58 publications

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“…Consequently, aldose reductase inhibitors were tested for their ability to improve endothelial dysfunction in experimental models of diabetes. Chronic oral treatment with structurally dissimilar aldose reductase inhibitors restored abnormal endothelium-dependent vasodilatation in all (Cameron & Cotter, 1992;Tesfamariam et al, 1993;Otter & Chess-Williams, 1994;Quilley et al, 1996) but one (Taylor et al, 1994b) study. The mechanisms responsible for the bene®cial e ects of aldose reductase inhibitors have not been elucidated, but several hypotheses have been formulated.…”

Section: Aetiology Of Endothelial Dysfunction In Diabetesmentioning

confidence: 95%

“…Whereas di erences in diabetes model and in duration or severity of diabetes undoubtedly play a role in some of the discrepancies, the type of circulation, the size of the vessel and the conditions of study may be a much more important source of disparity. This has been typically illustrated by the presence of impaired endothelium-dependent vasodilatation in vivo in the mesenteric circulation or in the isolated perfused mesentery of diabetic rats, and by its absence in the isolated aorta of the same animals (Fortes et al, 1983;Taylor et al, 1994b). Similarly, bradykinin-mediated vasodilatation was depressed in the hindquarters vasculature, but was normal in the kidney and mesenterium of the same diabetic rats (Ki et al, 1991).…”

Section: Mechanisms Of Impaired Endothelium-dependent Vasodilatation mentioning

confidence: 97%

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Endothelial dysfunction in diabetes

Vriese

Verbeuren

Voorde

et al. 2000

British J Pharmacology

1,015

769

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Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease. The endothelium controls the tone of the underlying vascular smooth muscle through the production of vasodilator mediators. The endothelium-derived relaxing factors (EDRF) comprise nitric oxide (NO), prostacyclin, and a still elusive endothelium-derived hyperpolarizing factor (EDHF). Impaired endothelium-dependent vasodilation has been demonstrated in various vascular beds of di erent animal models of diabetes and in humans with type 1 and 2 diabetes. Several mechanisms of endothelial dysfunction have been reported, including impaired signal transduction or substrate availibility, impaired release of EDRF, increased destruction of EDRF, enhanced release of endothelium-derived constricting factors and decreased sensitivity of the vascular smooth muscle to EDRF. The principal mediators of hyperglycaemia-induced endothelial dysfunction may be activation of protein kinase C, increased activity of the polyol pathway, non-enzymatic glycation and oxidative stress. Correction of these pathways, as well as administration of ACE inhibitors and folate, has been shown to improve endothelium-dependent vasodilation in diabetes. Since the mechanisms of endothelial dysfunction appear to di er according to the diabetic model and the vascular bed under study, it is important to select clinically relevant models for future research of endothelial dysfunction.

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Section: Aetiology Of Endothelial Dysfunction In Diabetesmentioning

confidence: 95%

Section: Mechanisms Of Impaired Endothelium-dependent Vasodilatation mentioning

confidence: 97%

Endothelial dysfunction in diabetes

Vriese

Verbeuren

Voorde

et al. 2000

British J Pharmacology

1,015

769

View full text Add to dashboard Cite

show abstract

“…For example the contractile responses to the application of norepinephrine in vascular smooth muscle of experimentally diabetic animals have exhibited increase [1,4,9,29], decrease [10,21] or no change [7,28]. Therefore, we used newly developed experimental diabetic animals, alloxan-induced diabetes-susceptible (ALS) and resistant (ALR) mice, to study changes in the function of the vascular smooth muscle in diabetes mellitus.…”

Section: Induction Of Diabetesmentioning

confidence: 99%

“…High K + -induced and 5-HT-induced contractions were unchanged at all times, while the maximum contraction induced by NE and the sensitivity of contractile response to PGF 2α increased in preparations from longer period diabetic animals. Many investigators have reported in various experimental conditions that NE-induced contraction was increased [1,4,9,29], decreased [10,21] or unchanged [7,28] in diabetic animals. In our study NE-induced contraction was indicated to be potentiated when animals were in a diabetic state for longer than 2 months.…”

Section: Changes Due To Diabetesmentioning

confidence: 99%

Vascular Responsiveness in Alloxan-Induced Diabetes-Susceptible (ALS) and Resistant (ALR) Mice.

Abe

Kawazoe

Kondo

et al. 1998

The Journal of Veterinary Medical Science

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ABSTRACT. Changes in reactivity of vascular smooth muscles of male alloxan-induced diabetes-susceptible (ALS) and resistant (ALR) mice aorta were investigated at 2 weeks, 1, 2 and 4 month(s) after the injection of alloxan (45 mg/kg, i.v.). The glucose levels in blood and urine of all the alloxan-treated ALS mice were markedly elevated while those in alloxan-treated ALR and non-treated ALS and ALR mice were not altered. The magnitude of high K + (65.4 mM)-induced contractions were not affected by the treatment of alloxan. Norepinephrine-induced contractions in vascular smooth muscles of ALS mice in a diabetic state for 2 or 4 months were significantly potentiated. The contractile sensitivity to prostaglandin F 2α (PGF 2α ) was increased in the 4 month-diabetic state. Responsiveness to 5-HT did not vary in the diabetic mouse. Vasorelaxation induced by nitroprusside was attenuated in 2 weeks, 2 or 4 month-diabetic ALS mice. Similarly the inhibitory effects of levcromakalim were attenuated at 2 and 4 months. The influences of diabetes on the inhibitory effects of forskolin or verapamil were very small or not detected. The effects of the vasomodulators used in this study on the vascular smooth muscles of alloxan-treated ALR mice did not differ from those of untreated ALR mice. The results from using ALS and ALR mice suggest that the vasoreactivities to some vasomodulators are changed especially in the long-term diabetic state and that when diabetes was not induced the dose of alloxan does not have any effect on vascular smooth muscle. -KEY WORDS: alloxan, diabetes mellitus, mouse, vascular smooth muscle.J. Vet. Med. Sci. 60(10): 1119-1125, 1998 with the same dose of alloxan, fell into a diabetic state. This study aimed to examine (1) the intrinsic differences in vascular functions between these two strains for which potential incidence of diabetes is genetically varied. Secondly, (2) diabetes-induced changes in the responses to vasostimulants and vasorelaxants in vascular smooth muscle of the ALS mouse were investigated. Furthermore (3) our research reports on the effect(s) of alloxan other than the induction of diabetes on vascular smooth muscle of ALR mouse at the dose which induces diabetes in ALS mouse but does not in ALR. MATERIALS AND METHODS Induction of diabetes:Zero point five% Alloxan was dissolved in sterilized 0.9% NaCl solution and used within 20 min. It was injected at a dose of 45 mg/kg into the caudal vein of male ALS and ALR mice aged 11 weeks. Control mice were administered 0.9% NaCl solution. Animals were used for experiment at 2 weeks, 1, 2 and 4 month(s) after the injection.Blood and urine glucose levels: Blood and urine glucose levels were measured by a glucose oxidase method and by a urine glucose test paper, respectively.

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“…Nas artérias mesentéricas in vivo e in vitro de animais diabéticos há redução da resposta induzida pela acetilcolina, enquanto que em aortas do mesmo animal essa resposta não se encontra alterada (FORTES et al, 1983b;TAYLOR et al, 1994). A duração do diabetes e o agonista usado também influenciam a resposta encontrada para agentes vasoconstritores e vasodilatadores.…”

Section: Palavras-chavesunclassified

Estudo das alterações da resposta vasodilatadora e vasoconstritora em aortas de ratas diabéticas e os mecanismos envolvidos.

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Endothelial function in the isolated perfused mesentery and aortae of rats with streptozotocin‐induced diabetes: effect of treatment with the aldose reductase inhibitor, ponalrestat

Cited by 64 publications

References 58 publications

Endothelial dysfunction in diabetes

Endothelial dysfunction in diabetes

Vascular Responsiveness in Alloxan-Induced Diabetes-Susceptible (ALS) and Resistant (ALR) Mice.

Estudo das alterações da resposta vasodilatadora e vasoconstritora em aortas de ratas diabéticas e os mecanismos envolvidos.

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