The effect of bradykinin on the oxidative state of rats with acute hyperglycaemia

Mikrut, Kinga; Paluszak, J; Koźlik, J; Sosnowski, Przemysław; Krauss, Hanna; Grześkowiak, Edmund

doi:10.1016/s0168-8227(00)00222-9

Cited by 36 publications

(25 citation statements)

References 29 publications

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“…In support of this possibility, we have shown that bradykinin reduces mitochondrial superoxide generation in human EA.hy926 vascular endothelial cells, an effect that is partly reversed by an NOS inhibitor (20). When bradykinin is administered to rats made hyperglycemic with streptozotocin (STZ), it also reduces their oxidative stress phenotype, as judged by hydrogen peroxide and malondialdehyde levels (46).…”

Section: Discussionmentioning

confidence: 85%

Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice

Kakoki¹,

Sullivan

Backus

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

110

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An insertion polymorphism of the angiotensin-I converting enzyme gene (ACE) is common in humans and the higher expressing allele is associated with an increased risk of diabetic complications. The ACE polymorphism does not significantly affect blood pressure or angiotensin II levels, suggesting that the kallikrein-kinin system partly mediates the effects of the polymorphism. We have therefore explored the influence of lack of both bradykinin receptors (B1R and B2R) on diabetic nephropathy, neuropathy, and osteopathy in male mice heterozygous for the Akita diabetogenic mutation in the insulin 2 gene (Ins2). We find that all of the detrimental phenotypes observed in Akita diabetes are enhanced by lack of both B1R and B2R, including urinary albumin excretion, glomerulosclerosis, glomerular basement membrane thickening, mitochondrial DNA deletions, reduction of nerve conduction velocities and of heat sensation, and bone mineral loss. Absence of the bradykinin receptors also enhances the diabetes-associated increases in plasma thiobarbituric acid-reactive substances, mitochondrial DNA deletions, and renal expression of fibrogenic genes, including transforming growth factor beta1, connective tissue growth factor, and endothelin-1. Thus, lack of B1R and B2R exacerbates diabetic complications. The enhanced renal injury in diabetic mice caused by lack of B1R and B2R may be mediated by a combination of increases in oxidative stress, mitochondrial DNA damage and over expression of fibrogenic genes.diabetes mellitus complications | kinins T he angiotensin-I converting enzyme (ACE) is a dipeptidyl carboxypeptidase, named because it removes two amino acids from the carboxyl terminus of the inactive peptide angiotensin I and converts it into the active blood pressure-raising peptide, angiotensin II. However, ACE is also a kininase and converts the active vasodilatory kinins into inactive metabolites by removing two amino acids from their carboxyl termini (1). Prior experimental findings (2) and computer simulations (3) show that modest changes in ACE levels affect the levels of its substrates much more than its products, indicating that relatively small changes in the levels of ACE affect kinin levels more than angiotensin II levels.The common insertion/deletion (I/D) polymorphism of the ACE gene in humans is due to the presence or absence of an Alu retrotransposon in the 16th intron of the gene. The polymorphism is associated with up to a twofold difference in relative plasma ACE levels (4), but the polymorphism does not significantly affect blood pressure or angiotensin II or aldosterone levels (5). Nevertheless, the I and D human ACE alleles are associated with different risks for developing diabetic complications including nephropathy (6

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Section: Discussionmentioning

confidence: 85%

Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice

Kakoki¹,

Sullivan

Backus

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

110

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“…•Ϫ (7,35), peroxynitrite (43), ⅐OH (41,45), and H 2 O 2 (36). Using the nonspecific fluorometric probe dichlorofluorescein (DCF), we (8) have previously observed an increase in ROS production in total diabetic mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Diabetic cardiomyopathy-associated dysfunction in spatially distinct mitochondrial subpopulations

Dabkowski¹,

Williamson²,

Bukowski³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

129

169

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Peer CJ, Callery PS, Hollander JM. Diabetic cardiomyopathy-associated dysfunction in spatially distinct mitochondrial subpopulations. Am J Physiol Heart Circ Physiol 296: H359 -H369, 2009. First published December 5, 2008 doi:10.1152/ajpheart.00467.2008.-Diabetic cardiomyopathy is the leading cause of heart failure among diabetic patients, and mitochondrial dysfunction has been implicated as an underlying cause in the pathogenesis. Cardiac mitochondria consist of two spatially, functionally, and morphologically distinct subpopulations, termed subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). SSM are situated beneath the plasma membrane, whereas IFM are embedded between myofibrils. The goal of this study was to determine whether spatially distinct cardiac mitochondrial subpopulations respond differently to a diabetic phenotype. Swiss-Webster mice were subjected to intraperitoneal injections of streptozotocin or citrate saline vehicle. Five weeks after injections, diabetic hearts displayed decreased rates of contraction, relaxation, and left ventricular developed pressures (P Ͻ 0.05 for all three). Both mitochondrial size (forward scatter, P Ͻ 0.01) and complexity (side scatter, P Ͻ 0.01) were decreased in diabetic IFM but not diabetic SSM. Electron transport chain complex II respiration was decreased in diabetic SSM (P Ͻ 0.05) and diabetic IFM (P Ͻ 0.01), with the decrease being greater in IFM. Furthermore, IFM complex I respiration and complex III activity were decreased with diabetes (P Ͻ 0.01) but were unchanged in SSM. Superoxide production was increased only in diabetic IFM (P Ͻ 0.01). Oxidative damage to proteins and lipids, indexed through nitrotyrosine residues and lipid peroxidation, were higher in diabetic IFM (P Ͻ 0.05 and P Ͻ 0.01, respectively). The mitochondria-specific phospholipid cardiolipin was decreased in diabetic IFM (P Ͻ 0.01) but not SSM. These results indicate that diabetes mellitus imposes a greater stress on the IFM subpopulation, which is associated, in part, with increased superoxide generation and oxidative damage, resulting in morphological and functional abnormalities that may contribute to the pathogenesis of diabetic cardiomyopathy. diabetes; free radical; mitochondria

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“…This may be particularly important under diabetic conditions. Its potential for NO-mediated reduction of oxygen radicals, for endothelium-dependent vasodilation, and for improvement of glucose transport and utilization make BK an important mediator for reducing the consequences of diabetes-related oxidative stress on both the myocardium and vessels (21). We and others have found that cardiac KLK mRNA expression and immunoreactivity as well as cardiac kininogen protein levels are reduced up to 40% in STZ-induced diabetic rats, and this therefore suggests that a reduced capacity for local generation of kinins might contribute to the pathogenesis of diabetic complications in this model.…”

Section: Discussionmentioning

confidence: 99%

Cardiac kinin level in experimental diabetes mellitus: role of kininases

Koch

Wendorf²,

Dendorfer³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Diabetes mellitus impairs the cardiac kallikrein-kinin system by reducing cardiac kallikrein (KLK) and kininogen levels, a mechanism that may contribute to the deleterious outcome of cardiac ischemia in this disease. We studied left ventricular (LV) function and bradykinin (BK) coronary outflow in buffer-perfused, isolated working hearts (n ϭ 7) of controls and streptozotocin (STZ)-induced diabetic rats before and after global ischemia. With the use of selective kininase inhibitors, the activities of angiotensin I-converting enzyme, aminopeptidase P, and neutral endopeptidase were determined by analyzing the degradation kinetics of exogenously administered BK during sequential coronary passages. Basal LV function and coronary flow were impaired in STZ-induced diabetic rats. Neither basal nor postischemic coronary BK outflow differed between control and diabetic hearts. Reperfusion after 15 min of ischemia induced a peak in coronary BK outflow that was of the same extent and duration in both groups. In diabetic hearts, total cardiac kininase activity was reduced by 41.4% with an unchanged relative kininase contribution compared with controls. In conclusion, despite reduced cardiac KLK synthesis, STZ-induced diabetic hearts are able to maintain kinin liberation under basal and ischemic conditions because of a primary impairment or a secondary downregulation of kinindegrading enzymes.bradykinin; kininase; myocardial ischemia AN INCREASE IN CARDIAC KININS might be a mechanism for protecting the heart during hypertension, cardiac failure, or acute myocardial infarction (MI). Several authors have reported increased endogenous levels of kallikrein (KLK), kininogen, and bradykinin (BK) and an upregulation of B 1 and B 2 receptors in response to cardiac ischemia (1,12,15,18,25,34,35). Direct application of BK in perfusion medium improves cardiac left ventricular (LV) function, coronary flow, and myocardial metabolism and reduces the infarct size of isolated working rat hearts during and after induction of myocardial ischemia via activation of the prostaglandin and nitric oxide (NO) axis (36). Likewise, the inhibition of kinin breakdown by kininase inhibitors has been shown to exert cardioprotective effects in in vivo models of MI (11,42).Several changes of the cardiac kallikrein-kinin system (KKS) have been found under diabetic conditions that may contribute to the profoundly altered myocardial and vascular integrity during the development of diabetic cardiopathy (30,31,38). Reduced effectiveness of exogenously applied BK on vascular dilation has been reported in diabetic subjects with endothelial dysfunction (14, 39). Moreover, we and others (30, 31, 38) have described reduced endogenous cardiac kininogen and KLK levels and/or alterations in the activation of cardiac tissue KLK in diabetic animals. Thus a reduction in the BK precursor content and in the activity of the BK-forming enzyme KLK may indicate a decreased capacity for generating cardiac BK and may be among the mechanisms involved in the development of coronary...

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The effect of bradykinin on the oxidative state of rats with acute hyperglycaemia

Cited by 36 publications

References 29 publications

Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice

Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice

Diabetic cardiomyopathy-associated dysfunction in spatially distinct mitochondrial subpopulations

Cardiac kinin level in experimental diabetes mellitus: role of kininases

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