Reduced expression of SK3 and IK1 channel proteins in the cavernous tissue of diabetic rats

Jun, Zhu; Jia, Ruipeng; Xu, Luwei; Wu, Jianping; Wang, Zizheng; Wang, Shukui; Bo, Cheng-Jia

doi:10.1038/aja.2009.97

Cited by 12 publications

(12 citation statements)

References 26 publications

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“…A reduced expression level of SK Ca and IK Ca associated to blunted EDHF-mediated relaxations has also been observed in the rat mesenteric artery following angiotensin II-induced hypertension [30] or common bile duct ligation [24], and in the rat cavernous tissue following streptozotocin-induced diabetes [31]. The present findings suggest that the beneficial effect of the RWPs treatment on the EDHF component might be due, at least in part, to their ability to restore the expression of SK Ca and IK Ca to a level similar to that observed in young adults.…”

Section: Discussionmentioning

confidence: 79%

Grape-Derived Polyphenols Improve Aging-Related Endothelial Dysfunction in Rat Mesenteric Artery: Role of Oxidative Stress and the Angiotensin System

Khodja¹,

Chataigneau²,

Auger³

et al. 2012

PLoS ONE

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Aging is characterized by the development of an endothelial dysfunction, which affects both the nitric oxide (NO)- and the endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations, associated with vascular oxidative stress and the activation of the angiotensin system. This study investigated whether red wine polyphenols (RWPs), antioxidants and potent stimulators of NO- and EDHF-mediated relaxations improve aging-related endothelial dysfunction, and, if so, examined the underlying mechanism. Mesenteric artery reactivity was determined in organ chambers, vascular oxidative stress by dihydroethidine and MitoSOX staining, and expression of target proteins by immunohistochemical staining. Control young rats (16 weeks) received solvent (ethanol, 3% v/v), and middle-aged rats (46 weeks) either solvent or RWPs (100 mg/kg/day) in the drinking water. The acetylcholine-induced endothelium-dependent NO component was slightly reduced whereas the EDHF component was markedly blunted in rings of middle-aged rats compared to young rats. The endothelial dysfunction was associated with oxidative stress, an upregulation of angiotensin II and AT1 receptors and a down-regulation of SKCa, IKCa, and angiotensin converting enzyme. Intake of RWPs for either one or two weeks improved the NO and the EDHF components of the relaxation, and normalized oxidative stress, the expression of SKCa, IKCa and the components of the angiotensin system. The protective effect of the 2-week RWPs treatment persisted for one and two weeks following stopping intake of RWPs. Thus, intake of RWPs caused a persistent improvement of the endothelial function, particularly the EDHF component, in middle-aged rats and this effect seems to involve the normalization of the expression of SKCa, IKCa and the angiotensin system.

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Section: Discussionmentioning

confidence: 79%

Grape-Derived Polyphenols Improve Aging-Related Endothelial Dysfunction in Rat Mesenteric Artery: Role of Oxidative Stress and the Angiotensin System

Khodja¹,

Chataigneau²,

Auger³

et al. 2012

PLoS ONE

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“…Diabetic neuropathy in mice is accompanied by glycocalyx alteration in brain microvessels (49). Finally, diabetes significantly reduces EDHmediated vasorelaxation in human penile resistance arteries and downregulates SK3 and IK1 channels in rat corpus cavernosum tissues (32). HYAL1 inhibition could thus be a first step to prevent loss of glycocalyx during the development of diabetic nephropathy, retinal microangiopathy, blood-brain barrier damage, and erectile dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes

et al. 2016

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Hyaluronic acid (HA) is a major component of the glycocalyx involved in the vascular wall and endothelial glomerular permeability barrier. Endocytosed hyaluronidase HYAL1 is known to degrade HA into small fragments in different cell types, including endothelial cells. In diabetes, the size and permeability of the glycocalyx are altered. In addition, patients with type 1 diabetes present increased plasma levels of both HA and HYAL1. To investigate the potential implication of HYAL1 in the development of diabetes-induced endothelium dysfunction, we measured endothelial markers, endothelium-dependent vasodilation, arteriolar glycocalyx size, and glomerular barrier properties in wild-type and HYAL1 knockout (KO) mice with or without streptozotocin (STZ)-induced diabetes. We observed that 4 weeks after STZ injections, the lack of HYAL1 1) prevents diabetes-induced increases in soluble P-selectin concentrations and limits the impact of the disease on endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation; 2) increases glycocalyx thickness and maintains glycocalyx structure and HA content during diabetes; and 3) prevents diabetes-induced glomerular barrier dysfunction assessed using the urinary albumin-to-creatinine ratio and urinary ratio of 70-to 40-kDa dextran. Our findings suggest that HYAL1 contributes to endothelial and glycocalyx dysfunction induced by diabetes. HYAL1 inhibitors could be explored as a new therapeutic approach to prevent vascular complications in diabetes.

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“…It has been reported that diabetes mellitus alters the aromatase enzyme in the gonadal tissues of rats, which may result into the induction of reproductive dysfunction (Burul-Bozkurt et al 2010). Diabetes inhibits mRNA and protein expression of both small (SK3) and intermediate (IK) conductance calcium-activated potassium channels in the cavernous tissue of diabetic rats, which could play a key role in the development of erectile dysfunction in diabetic rats (Zhu et al 2010). There are several reports in the literature that babies born to type I diabetic mothers are having altered growth and body composition, skeletal deformities as well as other abnormalities (Mughal et al 2010;Eidem et al 2010).…”

Section: Introductionmentioning

confidence: 97%

Enalapril reduces germ cell toxicity in streptozotocin-induced diabetic rat: investigation on possible mechanisms

Kushwaha

Jena

2011

Naunyn-Schmiedeberg's Arch Pharmacol

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Diabetes mellitus, a state of persistent hyperglycemia, is a major cause of micro- and macrovascular diseases. It affects nearly every system in the body including the reproductive system. Abnormalities in spermatogenesis and sexual function have been documented in animal models for both types of diabetes. The purpose of the present study is to determine the possible protective effects of enalapril against the germ cell toxicity in diabetic rat. Sprague-Dawley rats were divided into four groups: (1) control, (2) control + enalapril, (3) diabetic, and (4) diabetic + enalapril. Enalapril was administered per orally for 4 and 8 weeks continuously. After the treatment, animals were sacrificed and blood glucose level, sperm count, sperm DNA damage, apoptotic cell death, immunohistochemistry of 8-oxo- 7,8-dihydro- 2'-deoxyguanosine, and the cellular toxicity were performed. Furthermore, western blotting was performed to evaluate the expression of NFκB and COX-2 in testes. The results of the present study indicate that intervention of enalapril ameliorates the sperm DNA damage, reduces the oxidative stress, and down-regulates the expression of NFκB and COX-2 expression in streptozotocin-induced diabetic rat.

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Reduced expression of SK3 and IK1 channel proteins in the cavernous tissue of diabetic rats

Cited by 12 publications

References 26 publications

Grape-Derived Polyphenols Improve Aging-Related Endothelial Dysfunction in Rat Mesenteric Artery: Role of Oxidative Stress and the Angiotensin System

Grape-Derived Polyphenols Improve Aging-Related Endothelial Dysfunction in Rat Mesenteric Artery: Role of Oxidative Stress and the Angiotensin System

Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes

Enalapril reduces germ cell toxicity in streptozotocin-induced diabetic rat: investigation on possible mechanisms

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