Effects of vitamin E and sodium selenate on neurogenic and endothelial relaxation of corpus cavernosum in the diabetic mouse

Göçmen, Cemil; Secilmis, Ata; Kumcu, Eda Karabal; Ertuğ, Peyman U.; Önder, Serpil; Dikmen, Atilla; Baysal, Firuz

doi:10.1016/s0014-2999(00)00242-9

Cited by 56 publications

(10 citation statements)

References 27 publications

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“…Various antioxidants have been shown to improve endothelial function and erectile ability in animal models of diabetic erectile dysfunction (10,13,14). Adenovirus-mediated gene transfer of extracellular superoxide dismutase into the corpus cavernosum tissue was shown to reduce superoxide anion levels and raise cavernous cGMP levels, which resulted in partial recovery of erectile function in STZ-induced diabetic rats 2 days after transfection (14).…”

mentioning

confidence: 99%

Intracavernous Delivery of a Designed Angiopoietin-1 Variant Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse

et al. 2011

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OBJECTIVEPatients with diabetic erectile dysfunction often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. We examined the effectiveness of the potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous endothelial regeneration and restoring erectile function in diabetic animals.RESEARCH DESIGN AND METHODSFour groups of mice were used: controls; streptozotocin (STZ)-induced diabetic mice; STZ-induced diabetic mice treated with repeated intracavernous injections of PBS; and STZ-induced diabetic mice treated with COMP-Ang1 protein (days −3 and 0). Two and 4 weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations, Western blot analysis, and cGMP quantification. We also performed a vascular permeability test.RESULTSLocal delivery of the COMP-Ang1 protein significantly increased cavernous endothelial proliferation, endothelial nitric oxide (NO) synthase (NOS) phosphorylation, and cGMP expression compared with that in the untreated or PBS-treated STZ-induced diabetic group. The changes in the group that received COMP-Ang1 restored erectile function up to 4 weeks after treatment. Endothelial protective effects, such as marked decreases in the expression of p47phox and inducible NOS, in the generation of superoxide anion and nitrotyrosine, and in the number of apoptotic cells in the corpus cavernosum tissue, were noted in COMP-Ang1–treated STZ-induced diabetic mice. An intracavernous injection of COMP-Ang1 completely restored endothelial cell-cell junction proteins and decreased cavernous endothelial permeability. COMP-Ang1–induced promotion of cavernous angiogenesis and erectile function was abolished by the NOS inhibitor, N-nitro-L-arginine methyl ester, but not by the NADPH oxidase inhibitor, apocynin.CONCLUSIONSThese findings support the concept of cavernous endothelial regeneration by use of the recombinant Ang1 protein as a curative therapy for diabetic erectile dysfunction.

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confidence: 99%

Intracavernous Delivery of a Designed Angiopoietin-1 Variant Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse

et al. 2011

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“…We did not employ large doses or long‐term treatment of ascorbic acid; however, it has previously been suggested that a large dose of ascorbic acid may have pro‐oxidant effects, which warrants caution 15 . Previous reports suggest that different mechanisms may play a role in the NANC deficit in diabetic conditions 16–20 . We suggest that the inability of ascorbic acid to restore normal function of the diabetic corpus cavernosum nitrergic response is probably not because neuronal changes are irreversible at this stage of diabetes.…”

Section: Discussionmentioning

confidence: 99%

Effect of ascorbic acid treatment on endothelium‐dependent and neurogenic relaxation of corpus cavernosum from middle‐aged non‐insulin dependent diabetic rats

Gür¹,

Karahan

Öztürk

et al. 2005

Int J of Urology

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Aims : The purpose of the present study was to investigate functional responses and nitric oxide synthase activity in the corpus cavernosum of young control, middle-aged control and middle-aged non-insulin dependent diabetic rats. Methods : The animal groups were treated with ascorbic acid.Results : Acetylcholine-mediated endothelium-dependent relaxation of cavernosal tissue was significantly attenuated from a maximum of 58.0 ± 4.1% (1 mmol, n = 10) in young rats to 44.3 ± 1.6% in aged-matched controls (P < 0.05) and to 23.3 ± 2.8% in non-insulin-dependent diabetes mellitus rats (P < 0.01). These deficits in acetylcholine responsiveness were completely prevented by ascorbic acid treatment. Non-adrenergic non-cholinergic relaxations evoked by electrical field stimulation (0.5-64.0 Hz) in the corpus cavernosum of middle-aged control and non-insulin dependent (NID) diabetic rats are blunted and were not restored by ascorbic acid. The histochemical findings demonstrated a decrease of nicotinamide adenine dinucleotide phosphate-diaphorase staining in the cavernosal tissue obtained from middle-aged control rats and middle-aged diabetic rats. Conclusion : Partial correction by ascorbic acid may suggest the importance of reactive oxygen species and a therapeutic approach in impotent NID diabetic men.

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“…In addition, Cinar and colleagues (2001) showed in a 3-month model of diabetes a protective effect of 1000 mg of vitamin E/kg of chow against endothelial dysfunction. Similarly, a protective effect was shown in a mouse model (Göcmen et al, 2000) or in a 2-month rat model (Keegan et al, 1995). In support of these studies, Kunisaki and colleagues (1995) showed in a rat model that diabetes led to enhanced protein kinase C translocation and increased diacylglycerol formation, which both could be prevented by a 2-week vitamin E treatment in retinal vascular endothelial cells.…”

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confidence: 86%

Effect of Chronic Treatment with Vitamin E on Endothelial Dysfunction in a Type I in Vivo Diabetes Mellitus Model and in Vitro

Dhein

Kabat²,

Olbrich³

et al. 2003

J Pharmacol Exp Ther

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Diabetes mellitus often leads to generalized vasculopathy. Because of the pathophysiological role of free radicals we investigated the effects of vitamin E. Twenty-eight rats were rendered diabetic by streptozotocin injection and were fed either with a diet with low (10 mg/kg of chow), medium (75 mg/kg of chow) or high amounts of vitamin E (1300 mg/kg of chow). Nine age-matched nondiabetic rats receiving 75 mg of vitamin E/kg chow served as controls. After 7 months, mesenteric microcirculation was investigated. Smooth muscle contractile function was not altered in diabetic versus nondiabetic vessels. Endothelial function was significantly reduced in diabetics; relaxation upon 1 M acetylcholine was reduced by 50% in diabetics with a medium and high vitamin E diet. In vitamin E-deprived rats, a complete loss of endothelium-dependent relaxation was observed, and instead, acetylcholine elicited vasoconstriction. L-N G -Nitro-arginine-induced vasoconstriction was reduced in small arteries in diabetics, which was not prevented by vitamin E, but was aggravated by vitamin E deprivation. In a subchronic endothelial cell culture model, cells were cultivated with 5 or 20 mM D-glucose for an entire cell culture passage (4 days) with or without vitamin E (20 mg/l versus 0.01 mg/l). Hyperglycemia led to significant reduction in basal and ATP-stimulated nitric oxide (NO)-production. Hyperglycemia-induced reduction in basal NO-release was significantly prevented by vitamin E, whereas reduction in stimulated NO-release was not influenced. NADPH-diaphorase activity was reduced by 40% by hyperglycemia, which was completely prevented by vitamin E. We conclude that 1) vitamin E has a potential to prevent partially hyperglycemia-induced endothelial dysfunction, 2) under in vivo conditions vitamin E deficiency enhanced diabetic endothelial dysfunction dramatically, and 3) positive effects of vitamin E may be attenuated with a longer disease duration.

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Effects of vitamin E and sodium selenate on neurogenic and endothelial relaxation of corpus cavernosum in the diabetic mouse

Cited by 56 publications

References 27 publications

Intracavernous Delivery of a Designed Angiopoietin-1 Variant Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse

Intracavernous Delivery of a Designed Angiopoietin-1 Variant Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse

Effect of ascorbic acid treatment on endothelium‐dependent and neurogenic relaxation of corpus cavernosum from middle‐aged non‐insulin dependent diabetic rats

Effect of Chronic Treatment with Vitamin E on Endothelial Dysfunction in a Type I in Vivo Diabetes Mellitus Model and in Vitro

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