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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the past few years, a substantial body of evidence has accumulated that indicates hyperhomocysteinemia as a significant risk factor for cardiovascular disease. Hyperhomocysteinemia arises from a lack of key enzymes or vitamins such as methylenetetrahydrofolate reductase, vitamin B6, and folate which are involved in homocysteine metabolism. Heavy coffee consumption is also known to elevate homocysteine levels. The adverse effects associated with hyperhomocysteinemia are extensive. It increases risk of myocardial infarction, cardiovascular-related morbidity and mortality, peripheral vascular disease, atherosclerosis, coronary heart disease, and cerebrovascular disease. Its seriousness as a risk factor has been equated to hypercholesterolemia and smoking, two leading causes for cardiovascular disease. It also has been shown to produce a multiplicative effect with these and other risk factors such as hypertension. Two major hypotheses have been proposed to explain how homocysteine induces its harmful effects. It can damage endothelial cells lining the vasculature, allowing plaque formation. Simultaneously, it interferes with the vasodilatory effect of endothelial derived nitric oxide. Also, homocysteine has been found to promote vascular smooth muscle cells hypertrophy. Both of these processes induce vessel occlusion. Maintaining a normal plasma level of homocysteine as a means to prevent cardiovascular disease appears promising. This is achieved through increased intake of folate and vitamin B6 through diet or supplementation. Despite the overwhelming evidence suggesting homocysteine as a significant risk factor, no long-term prospective studies have been completed to demonstrate that folate and vitamin B6 can prevent cardiovascular disease related morbidity and mortality in patients with hyperhomocysteinemia. Homocysteine is a key metabolite in amino acid synthesis. During the process of methylation, S-adenosylmethionine (Ado Met), derived from methionine, is converted to S-Adenosylhomocysteine (Figure 1). This product is quickly hydrolyzed to form homocysteine and adenosine. Homocysteine can undergo 1 of 3 reactions depending on the status of the organism. If cysteine levels are inadequate, homocysteine utilizes the coenzyme pyridoxal phosphate (vitamin B6) to condense with serine, forming the intermediate cystathionine. Subsequent reactions with cystathionine lead to the formation of cysteine. When methionine levels are low, homocysteine is remethylated in a reaction involving the coenzyme N5-methyltetrahydrofolate or betaine. Finally, when both amino acids are in adequate supply, homocysteine is cleaved by the enzyme homocysteine desulthydrase (cystathionase) to form a-ketobutyrate, ammonia, and H2S. Thus, homocysteine's physiological role is to assist in maintaining sulfur-amino acid homeostasis. Beyond these metabolic processes, homocysteine is beginning to be recognized as a significant risk factor for cardiovascular disease including atherosclerosis, coronary artery disease, cerebrovascular disease, and myocardial infarction.
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PMID:Hyperhomocysteinemia: an additional cardiovascular risk factor. 1063 97

Hydrogen sulfide (H(2)S) is a newly found modulator in vascular system. This work showed that gene expression of cystathionine gamma-lyase (CSE), a H(2)S generating enzyme, and the activity of CSE in thoracic aorta were suppressed in hypertension rats. The plasma level of H(2)S also decreased in those rats. Exogenous administration of H(2)S could increase the plasma level of H(2)S and enhance the CSE activity of aorta. Exogenous administration of H(2)S also attenuated the elevation of pressure and lessened the aorta structural remodeling during the development of hypertension. In WKY rats, the gene expression and activity of CSE also decreased when the endogenous production of H(2)S was deprived by administration of DL-propargylglycine (specific inhibitor of CSE), accompanying the elevated pressure and the development of vascular remodeling. The results showed that endogenous H(2)S system was involved in both the maintenance of basal blood pressure and the development of hypertension. Exogenous H(2)S could exert beneficial effect on the pathogenesis of spontaneous hypertension.
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PMID:The possible role of hydrogen sulfide on the pathogenesis of spontaneous hypertension in rats. 1467 92

Hydrogen sulfide (H(2)S) may be endogenously produced by cystathionine beta-lyase (CBS) and cystathionine gamma-lyase (CSE) as a cardiovascular physiological functional factor. On the hypoxic pulmonary hypertension (HPH) animal model, the plasma H(2)S concentration, the gene expression and the activity (CSE) were decreased in lung tissues In L-NAME induced hypertension and spontaneous hypertension rats (SHR) models, the plasma H(2)S concentration, vascular CSE activity and mRNA expression were obviously decreased. When H(2)S was exogenously supplied, systolic pressure obviously decrease. These studies suggested that CSE/H(2)S pathway participated in the pathophysiological development of hypertension. The endogenous level of H(2)S produced by some arterial tissues increased in both septic and endotoxic shock rats. The level of H(2)S highly correlated with the endogenous level of NO. These results suggest that H(2)S may be a novel cardiovascular functional regulator.
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PMID:[Hydrogen sulfide: a novel cardiovascular functional regulatory gas factor]. 1497 Sep 1

Hydrogen sulfide (H(2)S) is a well-known toxic gas with the smell of rotten eggs. Recent studies have shown that H(2)S is generated in vivo in human and animal organisms and that it participates in many pathophysiological processes. H(2)S is produced endogenously in mammalian tissues from L-cysteine metabolism mainly by 3 enzymes: cystathionine beta-synthetase (CBS), cystathionine gamma-lyase (CSE) and 3-mercaptosulfurtransferase (MST). H(2)S may not only function as a neuromodulator in the central nervous system but it also relaxes gastrointestinal smooth muscles. More importantly, present evidence shows that H(2)S exerts regulatory effects on the pathogenesis of various cardiovascular diseases such as hypertension, pulmonary hypertension, shock and myocardial injury. The genomic basis of cystathioninuria in humans is 2 nonsense and 2 sense mutations in CSE. This review reveals that H(2)S is a new endogenous gaseous transmitter in the cardiovascular system.
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PMID:Hydrogen sulfide as a new endogenous gaseous transmitter in the cardiovascular system. 1647 73

Studies of nitric oxide over the past two decades have highlighted the fundamental importance of gaseous signaling molecules in biology and medicine. The physiological role of other gases such as carbon monoxide and hydrogen sulfide (H2S) is now receiving increasing attention. Here we show that H2S is physiologically generated by cystathionine gamma-lyase (CSE) and that genetic deletion of this enzyme in mice markedly reduces H2S levels in the serum, heart, aorta, and other tissues. Mutant mice lacking CSE display pronounced hypertension and diminished endothelium-dependent vasorelaxation. CSE is physiologically activated by calcium-calmodulin, which is a mechanism for H2S formation in response to vascular activation. These findings provide direct evidence that H2S is a physiologic vasodilator and regulator of blood pressure.
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PMID:H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. 1894 40

Impairment of the formation or action of hydrogen sulfide (H(2)S), an endogenous gasotransmitter, is associated with various diseases, such as hypertension, diabetes mellitus, septic and hemorrhagic shock, and pancreatitis. Cystathionine beta-synthase and cystathionine gamma-lyase (CSE) are two pyridoxal-5'-phosphate (PLP)-dependent enzymes largely responsible for the production of H(2)S in mammals. Inhibition of CSE by DL-propargylglycine (PAG) has been shown to alleviate disease symptoms. Here we report crystal structures of human CSE (hCSE), in apo form, and in complex with PLP and PLP.PAG. Structural characterization, combined with biophysical and biochemical studies, provides new insights into the inhibition mechanism of hCSE-mediated production of H(2)S. Transition from the open form of apo-hCSE to the closed PLP-bound form reveals large conformational changes hitherto not reported. In addition, PAG binds hCSE via a unique binding mode, not observed in PAG-enzyme complexes previously. The interaction of PAG-hCSE was not predicted based on existing information from known PAG complexes. The structure of hCSE.PLP.PAG complex highlights the particular importance of Tyr(114) in hCSE and the mechanism of PAG-dependent inhibition of hCSE. These results provide significant insights, which will facilitate the structure-based design of novel inhibitors of hCSE to aid in the development of therapies for diseases involving disorders of sulfur metabolism.
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PMID:Structural basis for the inhibition mechanism of human cystathionine gamma-lyase, an enzyme responsible for the production of H(2)S. 1901 29

The gas hydrogen sulfide (H2S) is emerging as a novel regulator of important physiologic functions such as arterial diameter, blood flow and leukocyte adhesion. In addition, it may have antiinflammatory and antiapoptotic effects. H2S has recently attracted much interest as a potent vasorelaxative substance that may establish itself alongside another gaseous signal molecule, nitric oxide (NO). In contrast to NO, the major source of H2S in blood may be production by red blood cells or by vascular smooth muscle cells. H2S is produced from cysteine, involving the enzymes cystathionine beta-synthase and cystathionine gamma-lyase (CSE). The importance of CSE was recently demonstrated in a mouse lacking CSE which showed reduced H2S levels and developed hypertension and reduced endothelium-mediated vasorelaxation. These data establish H2S as a new and important biologic signal molecule and as a new regulator of vascular blood flow and blood pressure.
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PMID:Hydrogen sulfide: a new gaseous signal molecule and blood pressure regulator. 1938 33

Hyperhomocysteinemia, an increased level of plasma homocysteine, is an independent risk factor for the development of premature arterial fibrosis with peripheral and cerebro-vascular, neurogenic and hypertensive heart disease, coronary occlusion and myocardial infarction, as well as venous thromboembolism. It is reported that hyperhomocysteinemia causes vascular dysfunction by two major routes: (1) increasing blood pressure and, (2) impairing the vasorelaxation activity of endothelial-derived nitric oxide. The homocysteine activates metalloproteinases and induces collagen synthesis and causes imbalances of elastin/collagen ratio which compromise vascular elastance. The metabolites from hyperhomocysteinemic endothelium could modify components of the underlying muscle cells, leading to vascular dysfunction and hypertension. Homocysteine metabolizes in the body to produce H(2)S, which is a strong antioxidant and vasorelaxation factor. At an elevated level, homocysteine inactivates proteins by homocysteinylation including its endogenous metabolizing enzyme, cystathionine gamma-lyase. Thus, reduced production of H(2)S during hyperhomocysteinemia exemplifies hypertension and vascular diseases. In light of the present information, this review focuses on the mechanism of hyperhomocysteinemia-associated hypertension and highlights the novel modulatory role of H(2)S to ameliorate hypertension.
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PMID:Homocysteine to hydrogen sulfide or hypertension. 2038 6

H(2)S, the most recently discovered gasotransmitter, might in fact be the evolutionary matriarch of this family, being both ancient and highly reduced. Disruption of gamma-cystathionase in mice leads to cardiovascular dysfunction and marked hypertension, suggesting a key role for this enzyme in H(2)S production in the vasculature. However, patients with inherited deficiency in gamma-cystathionase apparently do not present vascular pathology. A mitochondrial pathway disposes sulfide and couples it to oxidative phosphorylation while also exposing cytochrome c oxidase to this metabolic poison. This report focuses on the biochemistry of H(2)S biogenesis and clearance, on the molecular mechanisms of its action, and on its varied biological effects.
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PMID:Redox biochemistry of hydrogen sulfide. 2044 39

Hydrogen sulfide, H(2)S, is the third endogenous gas with cardiovascular properties, after nitric oxide and carbon monoxide. H(2)S is a potent vasorelaxant, and its deficiency is implicated in the pathogenesis of hypertension and atherosclerosis. Cystathionine beta-synthase, cystathionine gamma-lyase, and 3-mercaptopyruvate sulfurtransferase catalyze H(2)S formation. Chronic kidney disease is characterized by high prevalence of hyperhomocysteinemia, hypertension, and high cardiovascular mortality, especially in hemodialysis patients. H(2)S levels are decreased in hemodialysis patients through transcriptional deregulation of genes encoding for the H(2)S-producing enzymes. Potential implications relate to the pathogenesis of the manifestations of the uremic syndrome, such as hypertension and atherosclerosis.
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PMID:Hydrogen sulfide, the third gaseous signaling molecule with cardiovascular properties, is decreased in hemodialysis patients. 2079 58


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