Hydrogen sulfide is synthesized endogenously in both retinal artery and retina mostly via CSE

Hydrogen sulfide (H2S) is an important gasotransmitter expressed in various tissues of the organism, including the eye. It is known that H2S is localized especially in the retina and corneal layers in bovine eye. The enzymes that mediate H2S synthesis are 3-mercaptopyruvate sulfurtransferase (3-MST), cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). Herein, we aimed to investigate the concentration levels and distribution profiles of these enzymes in bovine retina and retinal artery. Enzyme levels were measured by ELISA and distribution were determined by immunofluorescence microscopic analysis. Much higher concentrations of CBS and CSE have been detected in the retinal artery compared to the retina. In both tissues, particulary 3-MST was found at the lowest level while, CSE was determined to be the most abundant enzyme among the others. CBS distribution was shown in both endothelial and smooth muscle layers, while CSE was seen especially in the endothelial layer of the retinal artery. In the retina, CBS and CSE were expressed in cone-basil cells and retinal ganglion cells, while CSE was also present in bipolar cells. Our results indicated that H2S is synthesized endogenously in ocular tissues. The widespread expression of H2S synthesizing enzymes in the retina and retinal artery of the bovine eye, which has anatomical similarities with the human eye, may suggest a protective role for H2S against retinal vascular diseases as well as a regulatory role in the retinal vascular tone

Caveolae depletion contributes to impaired relaxation induced by hydrogen sulfide in isolated human saphenous vein

3rd European Conference on the Biology of Hydrogen Sulfide (H2S) -- MAY 03-06, 2015 -- Athens, GREECEWOS: 00035331390005

Resveratrol improves high-fructose-induced vascular dysfunction in rats

High levels of fructose in the diet results in metabolic abnormalities and vascular disorders. In this study, the effect of resveratrol (RES) on vascular relaxation and contraction responses was examined in the aorta of high-fructose (HFr)-fed rats. mRNA expressions of aortic sirtuin 1 (SIRT1), GLUT5, and aldolase B were also investigated. Rats were given fructose (30%) and (or) RES (50 mg.L-1) in their drinking water for 8 weeks. In the HFr-fed rats, plasma levels of arginine and the ratio of arginine: asymmetric dimethylarginine (ADMA) decreased, whereas leptin levels increased. Decreased relaxation and increased contractile responses were detected in aortic rings. However, the aortic expressions of SIRT1, GLUT5, and aldolase B remained unchanged. RES treatment restored HFr-induced vascular dysfunction without improvements in insulin resistance. Treatment of HFr-fed rats with RES increased plasma levels of arginine and the L-arginine: ADMA ratio, and decreased plasma levels of leptin. RES increased SIRT1 expression, but decreased the expression of GLUT5 and aldolase B in aortas from HFr-fed rats. These results suggest that RES contributes to the restoration of HFr-induced vascular dysfunction in rats, at least in part, by up-regulation of SIRT 1 and down-regulation of GLUT5 and aldolase B in the aorta. Moreover, RES may have a positive influence on vasculature by partly restoring the plasma arginine: ADMA ratio and leptin levels

Control of human vascular tone by prostanoids derived from perivascular adipose tissue

Perivascular adipose tissue (PVAT) surrounds most vessels and has now been recognized as a regulator of vascular functions. This effect of PVAT has been mostly demonstrated in vessels obtained from rats and mice. Thus, the aim of this study was to investigate anti-contractile effect of PVAT surrounding human coronary bypass grafts such as saphenous vein (SV) and internal mammary artery (IMA). Moreover, we aimed to determine the involvement of prostanoids in the anticontractile effect of PVAT. Human SV and IMA preparations were set up in an organ bath. The presence of PVAT in SV and IMA preparations significantly attenuated the contractile response to noradrenaline (NA). Preincubation with indomethacin, a cyclooxygenase inhibitor, increased NA contraction in SV preparations with PVAT. This effect was not observed in IMA preparation with PVAT incubated with indomethacin. The lower measurements of prostaglandin E-2 (PGE(2)) released from PVAT surrounding IMA versus SV supported these effects. In conclusion, our results show that PVAT of SV could attenuate NA-induced contraction by releasing both PGE(2) and prostacyclin (PGI(2)). In contrast to SV, PVAT of IMA exerts its anti-contractile effect independently from prostanoids. These observations suggest that retaining PVAT in human SV and IMA preparations may have potential clinical implications to improve coronary bypass graft patency. (C) 2013 Elsevier Inc. All rights reserved

Vascular function and arginine and dimethylarginines in gentamicin-induced renal failure: A possible effect of heme oxygenase-1 inducer hemin

Increased oxidative stress and disturbance in nitric oxide bioavailability lead to endothelial dysfunction and cardiovascular complication in renal disease. Gentamicin (GM), a commonly used antibiotic exhibits a toxic effect on renal proximal tubules. Prevention of its nephrotoxicity is important. Therefore, we investigated whether heme oxygenase (HO)-1 induction influenced kidney and vascular function in GM-administered rats. GM (100 mg/kg/day; ip) was given to rats alone or together with hemin (20 mg/kg/alternate days; ip.) for 14 days. Plasma and kidney L-arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) as well as kidney 4-hydroxynonenal (HNE) levels and myeloperoxidase (MPO) activity were measured. Histopathologic examinations of kidney and relaxation and contraction responses of aorta were also examined. GM increased serum SDMA, urea nitrogen (BUN), and creatinine levels and caused histopathologic alterations in kidney. GM elevated HO-1 protein and mRNA expressions, 4-HNE level, MPO activity and decreased antioxidant enzyme activities and L-arginine levels in kidney. Decreased relaxation and contraction were detected in the aorta. Hemin restored renal oxidative stress and inflammatory changes together with vascular dysfunction, but did not affect SDMA, BUN, and creatinine levels. It is concluded that HO-1 induction may be effective in improving renal oxidative stress, inflammation and vascular dysfunction mediated by GM.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Effects of Crataegus microphylla on Vascular Dysfunction in Streptozotocin-induced Diabetic Rats

Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease. In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla (CM) extract in diabetic rats induced with streptozotocin (STZ, intraperitoneal, 65mg/kg) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase (iNOS), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action. Starting at 4weeks of diabetes, CM extract (100mg/kg) was administrated to diabetic rats for 4weeks. In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor- (TNF-) and interleukin-6 (IL-6), total nitritenitrate, and malondialdehite levels were increased in diabetic rats compared with controls. Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of diabetic rats with N-[3(aminomethyl) benzyl]-acetamidine, dihydrochloride (105M), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity. These results suggest that chronic in vivo treatment of CM preserves endothelium-dependent relaxation and vascular contraction in STZ-induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF- and IL-6 and by preventing lipid peroxidation. Copyright (c) 2012 John Wiley & Sons, Ltd

Acute simvastatin inhibits K-ATP channels of porcine coronary artery myocytes

Background: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors) consumption provides beneficial effects on cardiovascular systems. However, effects of statins on vascular KATP channel gatings are unknown.\ud \ud Methods: Pig left anterior descending coronary artery and human left internal mammary artery were isolated and endothelium-denuded for tension measurements and Western immunoblots. Enzymatically-dissociated/cultured arterial myocytes were used for patch-clamp electrophysiological studies and for [Ca²⁺]ᵢ, [ATP]ᵢ and [glucose](o) uptake measurements.\ud \ud Results: The cromakalim (10 nM to 10 μM)- and pinacidil (10 nM to 10 μM)-induced concentration-dependent relaxation of porcine coronary artery was inhibited by simvastatin (3 and 10 μM). Simvastatin (1, 3 and 10 μM) suppressed (in okadaic acid (10 nM)-sensitive manner) cromakalim (10 mM)-and pinacidil (10 μM)-mediated opening of whole-cell K-ATP channels of arterial myocytes. Simvastatin (10 mu M) and AICAR (1 mM) elicited a time-dependent, compound C (1 μM)-sensitive [H-3]-2-deoxy- glucose uptake and an increase in [ATP]ᵢ levels. A time (2-30 min)- and concentration (0.1-10 μM)-dependent increase by simvastatin of p-AMPKα-Thr¹⁷² and p-PP2A-Tyr³⁰⁷ expression was observed. The enhanced p-AMPK alpha-Thr¹⁷² expression was inhibited by compound C, ryanodine (100 μM) and KN93 (10 μM). Simvastatin-induced p-PP2A-Tyr³⁰⁷ expression was suppressed by okadaic acid, compound C, ryanodine, KN93, phloridzin (1 mM), ouabain (10 μM), and in [glucose](o)-free or [Na+](o)-free conditions.\ud \ud Conclusions: Simvastatin causes ryanodine-sensitive Ca²⁺ release which is important for AMPKα-Thr¹⁷² phosphorylation via Ca²⁺/CaMK II.AMPKα-Thr¹⁷² phosphorylation causes [glucose](o) uptake (and an [ATP]ᵢ increase), closure of K-ATP channels, and phosphorylation of AMPK alpha-Thr¹⁷² and PP2A-Tyr³⁰⁷ resulted. Phosphorylation of PP2A-Tyr³⁰⁷ occurs at a site downstream of AMPKα-Thr¹⁷² phosphorylation