Na+/H+ exchange inhibition with cariporide prevents alterations of coronary endothelial function in streptozotocin-induced diabetes

Vial, Guillaume; Dubouchaud, Hervé; Couturier, Karine; Lanson, Martine; Leverve, Xavier; Demaison, Luc

doi:10.1007/s11010-007-9669-1

Cited by 21 publications

(5 citation statements)

References 40 publications

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“…In our study, DM impaired endothelium independent relaxation that is in accordance with other reports (27-29). Since relaxation to SNP (NO donor) was shown to be impaired, it is possible that vascular smooth muscle did not respond to NO.…”

Section: Discussionsupporting

confidence: 94%

Co-administration of Grape Seed Extract and Exercise Training Improves Endothelial Dysfunction of Coronary Vascular Bed of STZ-Induced Diabetic Rats

Badavi¹,

Abedi²,

Sarkaki³

et al. 2013

Iran Red Crescent Med J

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BackgroundOne of the known complications of diabetes mellitus is vascular dysfunction. Inability of the coronary vascular response to cardiac hyperactivity might cause a higher incidence of ischemic heart disease in diabetic subjects. It has been indicated that regular exercise training and antioxidants could prevent diabetic cardiovascular problems enhanced by vascular damage.ObjectivesThe aim of this study was to determine the effects of grape seed extract (as antioxidant), with and without exercise training on coronary vascular function in streptozotocin induced diabetic rats.Materials and MethodsFifty male Wistar rats weighing 200 – 232 grams were randomly divided into five groups of 10 rats each: sedentary control, sedentary diabetic, trained diabetic, grape seed extract (200 mg/kg) treated sedentary diabetic and, grape seed extract treated trained diabetic. Diabetes was induced by one intraperitoneal injection of streptozotocin. After eight weeks, coronary vascular responses to vasoactive agents were determined.ResultsThe endothelium dependent vasorelaxation to acetylcholine was reduced significantly in diabetic animals; exercise training or grape seed extract administration partially improves this response. However, exercise training in combination with grape seed extract restores endothelial function completely. The endothelium independent vasorelaxation to sodium nitroprusside was improved by combination of exercise training and grape seed extract. On the other hand, the basal perfusion pressure and vasoconstrictive response to phenylephrine did not change significantly.ConclusionsThe data indicated that co-administration of grape seed extract and exercise training had more significant effects than exercise training or grape seed extract alone; this may constitute a convenient and inexpensive therapeutic approach to diabetic vascular complications.

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Section: Discussionsupporting

confidence: 94%

Co-administration of Grape Seed Extract and Exercise Training Improves Endothelial Dysfunction of Coronary Vascular Bed of STZ-Induced Diabetic Rats

Badavi¹,

Abedi²,

Sarkaki³

et al. 2013

Iran Red Crescent Med J

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“…However, this status is transient: heart failure inexorably develops [ 6 ] due to the progressive development of post-prandial hyperglycemia and oxidative stress. These changes alter coronary microvessel function [ 7 ], reduce myocardial perfusion and decrease cardiac mechanical function.…”

Section: Introductionmentioning

confidence: 99%

Dietary canolol protects the heart against the deleterious effects induced by the association of rapeseed oil, vitamin E and coenzyme Q10 in the context of a high-fat diet

et al. 2018

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BackgroundObesity progressively leads to cardiac failure. Omega-3 polyunsaturated fatty acids (PUFA) have been shown to have cardio-protective effects in numerous pathological situations. It is not known whether rapeseed oil, which contains α-linolenic acid (ALA), has a similar protective effect. Omega-3 PUFAs are sensitive to attack by reactive oxygen species (ROS), and lipid peroxidation products could damage cardiac cells. We thus tested whether dietary refined rapeseed oil (RSO) associated with or without different antioxidants (vitamin E, coenzyme Q10 and canolol) is cardio-protective in a situation of abdominal obesity.MethodsSixty male Wistar rats were subdivided into 5 groups. Each group was fed a specific diet for 11 weeks: a low-fat diet (3% of lipids, C diet) with compositionally-balanced PUFAs; a high-fat diet rich in palm oil (30% of lipids, PS diet); the PS diet in which 40% of lipids were replaced by RSO (R diet); the R diet supplemented with coenzyme Q10 (CoQ10) and vitamin E (RTC diet); and the RTC diet supplemented with canolol (RTCC diet). At the end of the diet period, the rats were sacrificed and the heart was collected and immediately frozen. Fatty acid composition of cardiac phospholipids was then determined. Several features of cardiac function (fibrosis, inflammation, oxidative stress, apoptosis, metabolism, mitochondrial biogenesis) were also estimated.ResultsAbdominal obesity reduced cardiac oxidative stress and apoptosis rate by increasing the proportion of arachidonic acid (AA) in membrane phospholipids. Dietary RSO had the same effect, though it normalized the proportion of AA. Adding vitamin E and CoQ10 in the RSO-rich high fat diet had a deleterious effect, increasing fibrosis by increasing angiotensin-2 receptor-1b (Ag2R-1b) mRNA expression. Overexpression of these receptors triggers coronary vasoconstriction, which probably induced ischemia. Canolol supplementation counteracted this deleterious effect by reducing coronary vasoconstriction.ConclusionCanolol was found to counteract the fibrotic effects of vitamin E + CoQ10 on cardiac fibrosis in the context of a high-fat diet enriched with RSO. This effect occurred through a restoration of cardiac Ag2R-1b mRNA expression and decreased ischemia.

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“…Hyperglycemia is associated with stimulation of Na+/ H+-exchanger-1 [22,38]. In the diabetic kidney it has been demonstrated that Na+/H+-exchanger-3 activity is increased [22].…”

Section: Discussionmentioning

confidence: 99%

“…Hyperglycemia and increased metabolic rate could accentuate proton production and lead to increased proton efflux through Na+/H+ exchange, which would stimulate Na + /Ca 2+ exchange and calcium overload [38]. Imbalance of sodium and calcium with hyperglycemia is associated with endothelial dysfunction and apoptosis [38], proliferation of vascular smooth muscle cells [43], retinal microangiopathy and ischemic damage [18,44], and myocardial damage [45][46][47]. It has been shown that inhibition of Na+/H+-exchanger-1 yields beneficial effects on diabetes vascular, retinal and renal complications but until our studies no information was available whether inhibiting Na+/H+-exchanger-1 improves diabetic peripheral neuropathy [10,18,22].…”

Section: Discussionmentioning

confidence: 99%

Treatment of peripheral diabetic neuropathy in Zucker diabetic fatty (ZDF) rats with cariporide

Lupachyk¹,

Shevalye²,

Watcho³

et al. 2014

JDM

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To determine the effect of Na+/H+-exchanger-1 on diabetic neuropathy in Type 2 diabetes Zucker diabetic fatty (ZDF) rats and lean controls were treated with cariporide (10 or 20 mg/kg/d), a Na+/H+-exchanger-1 inhibitor, for 4 weeks at 15 weeks of age. Neuropathy endpoints included motor (MNCV) and sensory (SNCV) nerve conduction velocities, thermal nociception, tactile allodynia and intraepidermal nerve fiber density. Advanced glycation endproduct and markers of oxidative stress including nitrated protein levels in sciatic nerve and dorsal root ganglion were also evaluated. Expression of Na+/H+-exchanger-1 in dorsal root ganglion neurons was increased in ZDF rats. At 15 weeks of age ZDF rats displayed hyperglycemia, MNCV and SNCV deficits, thermal hypoalgesia and tactile allodynia. At 20 but not 10 mg/kg/d, cariporide significantly improved MNCV and SNCV deficits, thermal hypoalgesia and tactile allodynia. Cariporide treatment was also associated with reduction of diabetes-induced accumulation of advanced glycation end-product (AGE), oxidative stress and nitrated proteins in sciatic nerve and dorsal root ganglion neurons. In conclusion, these findings support an important role for Na+/H+exchanger-1 in peripheral diabetic neuropathy, and provide rationale for development of Na+/ H+-exchanger-1 inhibitors for treatment of diabetic neural complications.

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Na+/H+ exchange inhibition with cariporide prevents alterations of coronary endothelial function in streptozotocin-induced diabetes

Cited by 21 publications

References 40 publications

Co-administration of Grape Seed Extract and Exercise Training Improves Endothelial Dysfunction of Coronary Vascular Bed of STZ-Induced Diabetic Rats

Co-administration of Grape Seed Extract and Exercise Training Improves Endothelial Dysfunction of Coronary Vascular Bed of STZ-Induced Diabetic Rats

Dietary canolol protects the heart against the deleterious effects induced by the association of rapeseed oil, vitamin E and coenzyme Q10 in the context of a high-fat diet

Treatment of peripheral diabetic neuropathy in Zucker diabetic fatty (ZDF) rats with cariporide

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