Changes in endothelium-dependent relaxation and levels of cyclic nucleotides in the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats

Abiru, Toichi; Watanabe, Yohko; Kamata, Katsuo; Kasuya, Yutaka

doi:10.1016/0024-3205(93)90616-b

Cited by 46 publications

(35 citation statements)

References 14 publications

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“…Impaired endothelium-dependent relaxation in aortas from diabetic animals has been extensively documented [5,6). In our study, we confirm the presence of vascular dysfunction and show that this occurs in the absence of overt morphological changes.…”

Section: Discussionsupporting

confidence: 87%

Gene transfer of endothelial nitric oxide synthase alters endothelium-dependent relaxations in aortas from diabetic rabbits

et al. 2000

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Cardiovascular disease is responsible for most of the excess mortality associated with diabetes mellitus [1], and impaired endothelium-dependent relaxation has been described in humans and in animal models of the disease [2±6]. A variety of mechanisms have been proposed to explain this observation and, in particular, the role of nitric oxide (NO) has been evaluated. Nitric oxide production has been reported to be either increased [7] or decreased [8] in the presence of high glucose concentrations. Moreover, endothelial dysfunction following hyperglycaemia is associated with increased generation of oxygen free radicals [9] and vasoconstrictor prostanoids [10,11]. The observation that diabetes-induced abnormalities of vascular relaxation are reversed when the vessel segments are exposed to indomethacin in the organ Diabetologia (2000) Abstract Aims/hypothesis. Cardiovascular disease is the leading cause of death in diabetes mellitus. Abnormal endothelium-dependent relaxation is observed both in humans and in animal models of diabetes mellitus and decreased bioavailability of nitric oxide (NO) is thought to be involved in this defect. Therefore, the aim of this study was to test whether adenovirus-mediated gene transfer of endothelial nitric oxide synthase (eNOS) alters vascular reactivity of diabetic vessels. Methods. Vascular reactivity was first assessed in thoracic aortas and carotid arteries from nine alloxan-induced diabetic (plasma glucose, 26.5 ± 1.2 mmol/l; HbA 1 c , 6.4 ± 0.3 %) and nine control rabbits (plasma glucose, 11.1 ± 1.3 mmol/l; HbA 1 c , 2.1 ± 0.1 %). Vascular reactivity was next examined in thoracic aortas of diabetic animals after ex vivo transduction with replication-deficient adenovirus encoding gene for eNOS (AdeNOS) or b-galactosidase (Adbgal).Results. After 10 weeks of hyperglycaemia, endothelium-dependent relaxation to acetylcholine was impaired in diabetic aorta, but was normal in carotid arteries from diabetic rabbits. In contrast, responses of both vessels to calcium ionophore and nitric oxide donor were normal. Histochemical staining for b-galactosidase and immunohistochemistry for eNOS showed transgene expression in the endothelium and adventitia in Adbgal and AdeNOS transduced vessels, respectively. During submaximum contractions with phenylephrine, relaxations to low concentrations of acetylcholine (3 10 ±8 to 10 ±7 mol/l) were augmented in AdeNOS transduced diabetic vessels. Conclusion/interpretation. These findings suggest that adenovirus-mediated gene transfer of eNOS to diabetic aorta alters vascular reactivity. [Diabetologia (2000) 43: 340±347]

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Section: Discussionsupporting

confidence: 87%

Gene transfer of endothelial nitric oxide synthase alters endothelium-dependent relaxations in aortas from diabetic rabbits

et al. 2000

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“…Compared with previous findings by our group and by others [13,16] there was a lesser effect of diabetes on ex vivo aortic relaxations observed in this study. A three-to fourfold rightward shift in the acetylcholine-induced relaxation occurred in previous studies [11,13,16], whereas for unknown reasons a smaller twofold shift occurred in this study.…”

contrasting

confidence: 80%

“…A three-to fourfold rightward shift in the acetylcholine-induced relaxation occurred in previous studies [11,13,16], whereas for unknown reasons a smaller twofold shift occurred in this study. Nonetheless, diabetes did cause a significant reduction in relaxation which was not significant in diabetic rabbits treated with gliclazide in vivo.…”

contrasting

confidence: 47%

“…The fact that responses to sodium nitroprusside are normal in diabetic rabbit aorta as found by us and others [13,16] compared with aberrant nitric oxide-induced responses in diabetes is perhaps explained by the different mechanism of action of sodium nitroprusside. That is, it enters the smooth muscle cell and then releases nitric oxide at the site of action [20], thereby avoiding any interstitial barriers, including superoxide anion.…”

mentioning

confidence: 54%

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Vascular action of the hypoglycaemic agent gliclazide in diabetic rabbits

et al. 1998

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“…The existence of such an action of vasoconstrictor prostanoids in the kidney is not supported by our study, inasmuch as cyclooxygenase-inhibition did not restore the blunted relaxations observed in the diabetic animals. Other investigations showed an impaired acetylcholine-induced cyclic GMP generation [7,8] or a restoration of the relaxation with l-arginine [9] or with free radical scavengers [10,11], suggesting a reduced availability or an increased destruction of endotheliumderived NO. Another study specifically found no evidence for an impaired EDHF release in diabetes [34].…”

Section: Basalmentioning

confidence: 99%

The impaired renal vasodilator response attributed to endothelium-derived hyperpolarizing factor in streptozotocin - induced diabetic rats is restored by 5-methyltetrahydrofolate

et al. 2000

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Dysfunction of the endothelium is an early and key event in the development of microvascular and macrovascular complications [1], which account for most of the morbidity and mortality of diabetes. Endothelial integrity is generally assessed by evaluating the vasodilator response of a blood vessel or a vascular bed to an endothelium-dependent agonist [2]. Endothelial cells relax the tone of the underlying vascular smooth muscle cells by releasing a number of vasodi- Diabetologia (2000) Abstract Aims/hypothesis. Endothelial dysfunction contributes to the development of diabetic vascular complications. A better understanding of the pathophysiology of endothelial dysfunction in diabetes could lead to new approaches to prevent microvascular disease. Methods. Endothelium-dependent and endotheliumindependent vasodilator responses were investigated in the renal microcirculation of streptozotocin-induced diabetic rats. We measured renal blood flow changes with an electromagnetic flow probe. In addition, the responses of the different segments of the renal microcirculation were evaluated with videomicroscopy using the hydronephrotic kidney technique. Because endothelial cells release different relaxing factors (nitric oxide, prostacyclin and an unidentified endothelium-derived hyperpolarizing factor), responses to acetylcholine were measured before and after treatment with the nitric oxide synthase inhibitor l-N G -nitroarginine methylester HCI (l-NAME) and the cyclooxygenase inhibitor indomethacin. We evaluated with the effect of 5-methyltetrahydrofolate, the active form of folate, on the responses. Results. The l-NAME-and indomethacin-resistant vasodilation to intra-renal acetylcholine was significantly reduced in the diabetic compared with control rats, suggesting impaired endothelium-derived hyperpolarizing factor-mediated vasodilation. The responses to the nitric oxide donor (Z)-1-[-2-(aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate) and to the K + -channel opener pinacidil were similar in diabetics and controls, indicating intact endothelium-independent vasodilator mechanisms. The contribution of endothelium-derived hyperpolarizing factor to vasodilation induced by acetylcholine was greatest in the smallest arterioles. In diabetic rats, the response to acetylcholine was increasingly impared as vessel size decreased. Defective vasodilation in diabetic kidneys was rapidly normalized by 5-methyltetrahydrofolate. Conclusion-interpretation. Endothelium-derived hyperpolarizing factor-mediated vasodilation is impaired in the renal microcirculation of diabetic rats, in particular in the smallest arteries. Treatment with folate restores the impaired endothelial function in diabetes. [Diabetologia (2000

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Changes in endothelium-dependent relaxation and levels of cyclic nucleotides in the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats

Cited by 46 publications

References 14 publications

Gene transfer of endothelial nitric oxide synthase alters endothelium-dependent relaxations in aortas from diabetic rabbits

Gene transfer of endothelial nitric oxide synthase alters endothelium-dependent relaxations in aortas from diabetic rabbits

Vascular action of the hypoglycaemic agent gliclazide in diabetic rabbits

The impaired renal vasodilator response attributed to endothelium-derived hyperpolarizing factor in streptozotocin - induced diabetic rats is restored by 5-methyltetrahydrofolate

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