Evaluation of the mechanism of endothelial dysfunction in the genetically-diabetic BB rat

Pieper, Galen M.; Moore-Hilton, Gail; Roza, Allan M.

doi:10.1016/0024-3205(95)02360-7

Cited by 59 publications

(42 citation statements)

References 20 publications

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“…There is now substantial evidence that endotheliumdependent vasodilation is abnormal in both conduit and resistance arteries of chemically induced experimental diabetic animals [Mayhan, 1989;Pieper and Gross, 1990;Mayhan et al, 1991;Diederich et al, 1994;Rosen et al, 1995;Taylor et al, 1995]. In two genetic models of IDDM, a similar impaired relaxation has been documented in the aorta [Durante et al, 1988;Pieper et al, 1996] and mesenteric arteries [Heygate et al, 1995;Lindsay et al, 1997] of diabetes-prone BB/W or BB/E rats. Similar results are reported for aorta and mesenteric arteries [Miyata et al, 1993] of the diabetes-prone WBN/Kob rat.…”

Section: Microvascular Dysfunction In Type-1 Diabetes Mellitusmentioning

confidence: 93%

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: Role of insulin and C‐peptide

Joshua

Zhang

Falcone

et al. 2005

J of Cellular Biochemistry

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Complications associated with insulin-dependent diabetes mellitus (type-1diabetes) primarily represent vascular dysfunction that has its origin in the endothelium. While many of the vascular changes are more accountable in the late stages of type-1diabetes, changes that occur in the early or initial functional stages of this disease may precipitate these later complications. The early stages of type-1diabetes are characterized by a diminished production of both insulin and C-peptide with a significant hyperglycemia. During the last decade numerous speculations and theories have been developed to try to explain the mechanisms responsible for the selective changes in vascular reactivity and/or tone and the vascular permeability changes that characterize the development of type-1diabetes. Much of this research has suggested that hyperglycemia and/or the lack of insulin may mediate the observed functional changes in both endothelial cells and vascular smooth muscle. Recent studies suggest several possible mechanisms that might be involved in the observed decreases in vascular nitric oxide (NO) availability with the development of type-1 diabetes. In addition more recent studies have indicated a direct role for both endogenous insulin and C-peptide in the amelioration of the observed endothelial dysfunction. These results suggest a synergistic action between insulin and C-peptide that facilitates increase NO availability and may suggest new clinical treatment modalities for type-1 diabetes mellitus.

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Section: Microvascular Dysfunction In Type-1 Diabetes Mellitusmentioning

confidence: 93%

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: Role of insulin and C‐peptide

Joshua

Zhang

Falcone

et al. 2005

J of Cellular Biochemistry

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“…Since no other vasodilator responses were tested, it is unclear whether this protective e ect was related to decreased NO quenching or to an aspeci®c improvement of vascular distensibility. Several authors found no bene®cial e ect of aminoguanidine on disordered endothelium-dependent vasodilatation in experimental diabetes (Hill & Ege, 1994;Pieper et al, 1996;Crijns et al, 1998). In contrast, aminoguanidine prevented diabetes-induced changes in arteriolar mechanical behaviour, as de®ned by decreased passive compliance and impaired myogenic reactivity of the arteriolar wall (Huijberts, et al, 1993;Hill & Ege, 1994).…”

Section: Aetiology Of Endothelial Dysfunction In Diabetesmentioning

confidence: 99%

“…Oxygen-derived free radicals may impair endotheliumdependent vasodilatation through inactivation of NO or by serving as an EDCF (Rubanyi & Vanhoutte, 1986;Katusic & Vanhoutte, 1989). Acute administration of scavengers of superoxide anion, including superoxide dismutase (Hattori et al, 1991;Tesfamariam & Cohen, 1992;Pieper et al, 1996;Bohlen & Lash, 1993) and the combination of superoxide dismutase with catalase (Pieper et al, 1997) improved or normalized the abnormal endothelium-dependent responses in di erent models of diabetes and during high glucose exposure. Similarly, chronic treatment with probucol (Tesfamariam & Cohen, 1992), N-acetylcysteine (Pieper & Siebeneich, 1998b), vitamin E (Keegan et al, 1995;RoÈ sen et al, 1996) and vitamin C (Ting et al, 1996) prevented the development of endothelial dysfunction in clinical and experimental diabetes.…”

Section: Aetiology Of Endothelial Dysfunction In Diabetesmentioning

confidence: 99%

Endothelial dysfunction in diabetes

Vriese

Verbeuren

Voorde

et al. 2000

British J Pharmacology

1,007

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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“…Descending thoracic aortae were carefully excised and excessive connective tissue and fat were removed. Segments of aorta were cut into rings and mounted on parallel wires in 10 ml isolated Radnoti tissue baths containing Krebs-Henseleit media as previously described [6]. Rings were contracted to an optimal resting tension of 2.0 g and equilibrated for 1 h. Isometric tension was measured using Radnoti force-displacement transducers and amplifiers connected to a Gould TA6000 recorder.…”

Section: : 910-915]mentioning

confidence: 99%

“…Currently, only a limited number of studies regarding endothelial function have been conducted in this important model [4][5][6][7]. More importantly, there is no available information regarding specific defects in nitric oxide (NO) production contributing to defective endothelium-dependent relaxation in this model.…”

mentioning

confidence: 99%

Reversal by L-arginine of a dysfunctional arginine/nitric oxide pathway in the endothelium of the genetic diabetic BB rat

et al. 1997

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Recent studies have indicated impaired endotheliumdependent relaxation in arteries of insulin-dependent [1] diabetic (IDDM) patients. The mechanisms for this defect in human blood vessels is not yet understood. Several studies have observed defects in endothelium-dependent relaxation in both conduit and resistance arteries of streptozotocin (STZ)-or alloxaninduced diabetic rats or rabbits (see reviews [2,3]).Another experimental diabetic model which is not as frequently investigated is the spontaneously diabetic BB (Bio-Breeding) rat despite the fact that this model more closely approximates IDDM in man. Currently, only a limited number of studies regarding endothelial function have been conducted in this important model [4][5][6][7]. More importantly, there is no available information regarding specific defects in nitric oxide (NO) production contributing to defective endothelium-dependent relaxation in this model. In this study, we evaluated the efficacy of supplementation with l -arginine (l-ARG) to improve NO synthase-dependent, endothelium-dependent relaxation in the diabetic BB rat. Materials and methodsExperiments were performed in compliance with the National Institutes of Health "Principles of Laboratory Animal Care" (NIH publication No. 85-23, revised 1985). Progeny of the original BB rat colony from the University of Pennsylvania were used in breeding pairs to develop a local colony of diabetic and non-diabetic BB rats. Onset of diabetes was regularly monitored using test strips and glucometer and defined by 2 successive days of elevated glucose concentration less than 11 mmol/l. Diabetic animals received s. c. injections of NPH insulin which was varied to maintain a low level of hyperglycaemia (i. e. approximately 12-14 mmol/l). Female diabetic BB rats and age-matched, diabetic-resistant littermates were Diabetologia (1997) 40: 910-915 Reversal by L-arginine of a dysfunctional arginine/nitric oxide pathway in the endothelium of the genetic diabetic BB rat Summary We examined the effects of acute supplementation with arginine in vitro on endothelium-dependent relaxation in aortic rings taken from female genetic, diabetes-prone BB rats. Sensitivity to norepinephrine-induced contraction was unaltered in rings of diabetic BB rats compared to rings from non-diabetic littermates. In precontracted rings, acetylcholine produced a concentration-dependent relaxation which was impaired by diabetes. This relaxation was blocked by l -arginine had no effect on acetylcholine-induced relaxation in control rings. In contrast, relaxation-induced by nitroglycerin in diabetic rings without endothelium was not altered by l -arginine treatment. Thus, a defect in the utilization of arginine by nitric oxide synthase exists in the endothelium of the diabetic BB rat. [Diabetologia (1997) 40: 910-915]

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Evaluation of the mechanism of endothelial dysfunction in the genetically-diabetic BB rat

Cited by 59 publications

References 20 publications

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: Role of insulin and C‐peptide

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: Role of insulin and C‐peptide

Endothelial dysfunction in diabetes

Reversal by L-arginine of a dysfunctional arginine/nitric oxide pathway in the endothelium of the genetic diabetic BB rat

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