Hydrogen sulfide (H2S) is an endogenous gas transmitter with profound effects on the cardiovascular system. We hypothesized that stimulation of H2S synthesis might alleviate age-associated changes in vascular reactivity. Pyridoxal-5-phosphate (PLP), the coenzyme of H2S-synthesizing enzymes, was administrated to old male Wistar rats per os at a dose of 0.7 mg/kg body mass once a day for 2 weeks. H2S content in the aortic tissue, markers of oxidative stress, inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS), arginase activities, and endothelium-dependent vasorelaxation of the aortic rings were studied. Our results showed that PLP restored endogenous H2S and low molecular weight S-nitrosothiol levels in old rat aorta to the levels detected in adults. PLP significantly reduced diene conjugate content, hydrogen peroxide and peroxynitrite generation rates, and iNOS and arginase activity in the aortic tissue of old rats. PLP also greatly improved acetylcholine-induced relaxation of old rat aorta (47.7% ± 4.8% versus 18.4% ± 4.1% in old rats, P < 0.05) that was abolished by NO inhibition with N-nitro-l-arginine methyl ester hydrochloride (L-NAME) or H2S inhibition with O-carboxymethylhydroxylamine (O-CMH). Thus, PLP might be used for stimulation of endogenous H2S synthesis and correction of oxidative and nitrosative stress and vessel tone dysfunction in aging and age-associated diseases.
Background Ageing is accompanied by a decrease in endogenous hydrogen sulphide (H2S) synthesis and the development of mitochondrial dysfunction. The aim of our work was to study the possible participation of exercise training‐induced regulation of endogenous H2S production in the restoration of mitochondrial function in old rats. Materials and Methods Male rats were divided into three groups: adult, old and exercise‐trained old. Exercise training of old rats was performed for 4 weeks. The mRNA expression cystathionine‐γ‐lyase (CSE) and 3‐mercaptopyruvate sulfurtransferase (3‐MST) were determined using reverse transcription and real‐time polymerase chain reaction analysis. Mitochondrial dysfunction was determined by mPTP opening, which was investigated by spectrophotometric registration of the swelling of mitochondria isolated from the rat heart. We also studied the effect of exercise on H2S content, oxidative stress and mtNOS activity. Results Exercise training in old animals significantly increased the expression of H2S‐synthesizing enzymes CSE and 3‐MST and restored endogenous H2S production in cardiac tissue and cardiac mitochondria to levels of adult animals. In addition, the training significantly reduced oxidative stress in old rats, in particular the rate of formation of •O2− and H2O2, diene conjugates and malondialdehyde levels in the mitochondria of the heart. Simultaneously, in the hearts of these animals, resistance of mPTP to the inducer of its opening of calcium ions was increased. Conclusions Thus, exercise training restores endogenous H2S production, and significantly reduces oxidative stress in cardiac mitochondria of old rats that are associated with the inhibition of calcium‐induced mPTP opening as an indicator of mitochondrial dysfunction.
Background:In the present work, we investigated the cardioprotective potential of pyridoxal-5-phosphate (PLP) in old rats as a cofactor of enzymes that synthesize hydrogen sulphide (H 2 S). Materials and methods:PLP was administered per os in a dose of 0.7 mg per kg daily for 2 weeks. Rats were divided into three groups (adult, old and old +PLP) of 20 animals. The cardiac mRNA levels of genes encoding H 2 S-synthesizing enzymes cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST), uncoupling proteins (UCP3), subunits of ATP-sensitive potassium (K ATP ) channels were determined using real-time polymerase chain reaction analysis.We also studied the effect of PLP-administration on the content of H 2 S, oxidative stress, the activities of inducible and constitutive NO-synthase (iNOS, cNOS), arginase and nitrate reductase in the heart homogenates as well as cardiac resistance to ischemia-reperfusion in Langendorff-isolated heart model. Results:It was shown that PLP restored mRNA levels of CSE, 3-MST and UCP3 genes, and H 2 S content and also significantly increased the expression of SUR2 and Kir6.1 (2.2 and 3.3 times, respectively) in the heart of old rats. PLP significantly reduced the formation of superoxide, malondialdehyde, diene conjugates as well as the activity of iNOS and arginase. PLP significantly increased constitutive synthesis of NO and prevented reperfusion disturbances of the heart function after ischemia.Conclusions: Thus, PLP-administration in old rats was associated with upexpression of CSE, 3-MST, UCP3 and SUR2 and Kir6.1 subunits of K ATP channels, and also increased cNOS activity and reduced oxidative stress and prevented reperfusion dysfunction of the heart in ischemia-reperfusion. K E Y W O R D Sageing, H 2 S-synthesizing enzymes, ischemia-reperfusion, K ATP channels, pyridoxal-5phosphate
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