Plasma endothelin levels and vascular responses at different temporal stages of streptozotocin diabetes

Hopfner, Rob L; McNeill, J. Robert; Gopalakrishnan, Venkat

doi:10.1016/s0014-2999(99)00316-7

Cited by 41 publications

(32 citation statements)

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“…Some works in streptozotocininduced diabetic rats do not report any impairment of endothelium-derived relaxations in isolated aortic segments during the first 2 weeks after diabetes was induced [49,50]. Using the same diabetic model, other studies on intestinal arterioles [43] or hindquarter haemodynamics [7] indicate endothelial dysfunction 8 to 14 days after streptozotocin administration.…”

Section: Discussionmentioning

confidence: 99%

Early and intermediate Amadori glycosylation adducts, oxidative stress, and endothelial dysfunction in the streptozotocin-induced diabetic rats vasculature

et al. 2003

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Aims/hypothesis. In a model of streptozotocin-induced Type 1 diabetes mellitus in rats of 9 weeks duration, we analysed time associations between the development of hyperglycaemia, early and intermediate glycosylation Amadori adducts, or AGE compared with enhancement of oxidative stress and endothelial dysfunction.Methods. Endothelial function was tested at several stages of streptozotocin-induced diabetes and after treatment with insulin, resulting in different concentrations of blood glucose, glycosylated haemoglobin (an Amadori adduct), and AGE. Other animals were studied antagonising the formation of AGE with aminoguanidine. Results. Relaxation in response to acetylcholine (1 nmol/l to 10 µmol/l) was tested in isolated segments from aorta or mesenteric microvessels. Impairment of endothelium-dependent relaxations occurred after 2 weeks of untreated diabetes. Preincubation of vessels affected with 100 U/ml superoxide dismutase improved the relaxations to acetylcholine, along the time-course of the endothelial impairment. This indicates the participation of reactive oxygen species on diabetic endothelial dysfunction. The impairment of endothelium-dependent relaxations was recovered after 3 more weeks of insulin treatment. Aminoguanidine treatment did not modify this pattern of development. The time course of the rise and disappearance of endothelial dysfunction showed a higher correlation with glycosylated haemoglobin concentrations than with blood glucose or serum AGE. Conclusion/interpretation. Enhancement of early and intermediate Amadori adducts of protein glycosylation was the factor showing a better relation with the development of endothelium impairment. These results are consistent with a role for these products in the development of diabetic vasculopathy. [Diabetologia (2003) 46:556-566] Keywords Diabetes mellitus, endothelial dysfunction, nitric oxide, superoxide anions, hyperglycaemia, Amadori adducts, advanced glycosylation end-products. Endothelial dysfunction seems to be a key factor in the development of diabetic vascular complications. The impairment of endothelium-dependent vasodilatations is an early event occurring in diabetic patients [1,2,3] and animal diabetic models [4,5,6, 7]. Enhanced oxidative stress in diabetes mellitus has been also shown [8,9], which can be detected by peroxidation products [10] or by increased generation of reactive oxygen species (ROS), mainly superoxide anions [11]. Indeed, enhanced oxidative stress is proposed to be a major cause of diabetic endothelial dysfunction [12,13].There is also increasing evidence that diabetic endothelial dysfunction and oxidative stress are a conse-

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Section: Discussionmentioning

confidence: 99%

Early and intermediate Amadori glycosylation adducts, oxidative stress, and endothelial dysfunction in the streptozotocin-induced diabetic rats vasculature

et al. 2003

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“…It has been widely reported that RAS is implicated in hemodynamic maladaptations of the diabetic kidney [21,22,28] , and the changes of ACE, ACE2, as well as Ang II, have been investigated in STZ-induced diabetic rats [23][24][25] . Previous investigations have shown that Ang (1-7) serves a protective role by counteracting the effects of locally-generated Ang II in cardiovascular research [26] .…”

Section: Discussionmentioning

confidence: 99%

Chronic angiotensin (17) injection accelerates STZ-induced diabetic renal injury¹

Shao

Zhou

et al. 2008

Acta Pharmacologica Sinica

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Aim: The renin-angiotensin system (RAS) plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. In the past few years, angiotensin (Ang) (1-7) has been reported to counteract the effects of Ang II and was even considered as a new therapeutical target in RAS. The present study aimed to investigate the effect of Ang (1-7) administration on a diabetic animal model and the modulation on local RAS. Methods: Streptozotocin (STZ) injection-induced diabetic rats were used in the experiment. The animals were divided into 3 groups: (1) control; (2) STZ-induced diabetes; and (3) STZ-induced diabetes with chronic Ang (1-7) treatment [D+Ang (1-7)]. In the D+Ang(1-7) group, a dose of 25 µg·kg of Ang (1-7) was continually injected through the jugular vein by embedding miniosmotic pump for 6 weeks. Plasma glucose, ratio of kidney to body weight, and 24 h urine protein and serum creatinine were monitored by conventional measurement. Plasma and renal Ang II levels were measured by radioimmunoassay. Ang-converting enzyme (ACE), ACE2, Ang II type 1 (AT1) receptor, Ang II type 2 (AT2) receptor, Ang (1-7) Mas receptor, and TGF-β1 mRNA levels were measured by real time PCR; ACE, ACE2, and TGF-β1 protein levels were analyzed by Western blotting. Results:The renal function of diabetic rats was significantly retrogressed when compared with that of control rats. After the treatment by constant Ang (1-7) vein injection for 6 weeks, renal function was found to be even worse than diabetic rats, and both TGF-β1 mRNA and protein levels were elevated in the D+Ang(1-7) group compared with the diabetic rats. The real-time PCR result also showed an increase in ACE mRNA expression and decrease in ACE2 mRNA level in the D+Ang(1-7) group when compared with diabetic rats. The number of AT1 receptors increased in the Ang (1-7)-injected group, while the number of AT2 and Mas receptors decreased. Conclusion: Exogenous Ang (1-7) injection did not ameliorate STZinduced diabetic rat renal injury; on the contrary, it accelerated the progressive diabetic nephropathies.

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“…Therefore, specifically the combination of DM and an atherogenic diet appears to alter ET-1 responsiveness. In contrast, other DM animal models have reported enhanced ET-1 vascular responsiveness (31,55,56), also in the coronary circulation (8,61). These differences between DM models are not readily explained but may involve differences in vascular beds (55,56), genetically modified strains (8,55,56), and different temporal stages of DMinduction with subsequent other metabolic alterations (31, 61).…”

Section: H90 Coronary Microvascular Dysfunction In a Porcine Dm Modelmentioning

confidence: 99%

Coronary microvascular dysfunction in a porcine model of early atherosclerosis and diabetes

Heuvel

Sorop

Koopmans

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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van den Heuvel M, Sorop O, Koopmans SJ, Dekker R, de Vries R, van Beusekom HM, Eringa EC, Duncker DJ, Danser AH, van der Giessen WJ. Coronary microvascular dysfunction in a porcine model of early atherosclerosis and diabetes. Am J Physiol Heart Circ Physiol 302: H85-H94, 2012. First published October 7, 2011 doi:10.1152/ajpheart.00311.2011.-Detailed evaluation of coronary function early in diabetes mellitus (DM)-associated coronary artery disease (CAD) development is difficult in patients. Therefore, we investigated coronary conduit and small artery function in a preatherosclerotic DM porcine model with type 2 characteristics. Streptozotocin-induced DM pigs on a saturated fat/cholesterol (SFC) diet (SFC ϩ DM) were compared with control pigs on SFC and standard (control) diets. SFC ϩ DM pigs showed DM-associated metabolic alterations and early atherosclerosis development in the aorta. Endothelium-dependent vasodilation to bradykinin (BK), with or without blockade of nitric oxide (NO) synthase, endothelium-independent vasodilation to an exogenous NO-donor (S-nitroso-N-acetylpenicillamine), and vasoconstriction to endothelin (ET)-1 with blockade of receptor subtypes, were assessed in vitro. Small coronary arteries, but not conduit vessels, showed functional alterations including impaired BKinduced vasodilatation due to loss of NO (P Ͻ 0.01 vs. SFC and control) and reduced vasoconstriction to ET-1 (P Ͻ 0.01 vs. SFC and control), due to a decreased ETA receptor dominance. Other vasomotor responses were unaltered. In conclusion, this model demonstrates specific coronary microvascular alterations with regard to NO and ET-1 systems in the process of early atherosclerosis in DM. In particular, the altered ET-1 system correlated with hyperglycemia in atherogenic conditions, emphasizing the importance of this system in DM-associated CAD development. coronary circulation; diabetes mellitus; endothelial function; endothelin-1 DIABETES MELLITUS (DM) IS widespread in industrialized countries, and the incidence of type 2 is rapidly increasing worldwide. DM is an independent and strong predictor of coronary artery disease (CAD) (26), characterized by atherosclerosis of the conduit arteries (16, 23) and dysfunction of the microcirculation (51). Endothelial dysfunction is an important determinant of altered vascular reactivity and plays a major role in the genesis of DM-induced macro-and microvascular complications (51). Impaired coronary vasodilation, which is present well before the development of angiographically visible atherosclerosis in DM patients, is known to be at least partially due to impairment of the nitric oxide (NO) system (45). On the other hand, it is less clear whether and how the vasoconstricting endothelin (ET)-1 system is affected. Evidence of an altered ET-1 system in DM patients is predominantly coming from studies in the peripheral circulation in advanced stages of disease (30), and details on coronary alterations in relation to ET-1 in DM subjects are scarce (48, 62), in particular in early CAD developmen...

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Plasma endothelin levels and vascular responses at different temporal stages of streptozotocin diabetes

Cited by 41 publications

References 32 publications

Early and intermediate Amadori glycosylation adducts, oxidative stress, and endothelial dysfunction in the streptozotocin-induced diabetic rats vasculature

Early and intermediate Amadori glycosylation adducts, oxidative stress, and endothelial dysfunction in the streptozotocin-induced diabetic rats vasculature

Chronic angiotensin (17) injection accelerates STZ-induced diabetic renal injury¹

Coronary microvascular dysfunction in a porcine model of early atherosclerosis and diabetes

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Plasma endothelin levels and vascular responses at different temporal stages of streptozotocin diabetes

Cited by 41 publications

References 32 publications

Early and intermediate Amadori glycosylation adducts, oxidative stress, and endothelial dysfunction in the streptozotocin-induced diabetic rats vasculature

Early and intermediate Amadori glycosylation adducts, oxidative stress, and endothelial dysfunction in the streptozotocin-induced diabetic rats vasculature

Chronic angiotensin (17) injection accelerates STZ-induced diabetic renal injury1

Coronary microvascular dysfunction in a porcine model of early atherosclerosis and diabetes

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Chronic angiotensin (17) injection accelerates STZ-induced diabetic renal injury¹