Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary supplementation of L-arginine, the precursor of endogenous NO, has been shown to enhance endothelial function in the cholesterol-fed rabbits. However, the mechanism by which dietary L-arginine accomplishes these effects has been unclear. In the present study we have assessed the plasma concentrations of L-arginine and of asymmetrical dimethylarginine (ADMA), a known endogenous inhibitor of NO synthase, in cholesterol-fed rabbits with or without dietary supplementation of L-arginine. Urinary nitrate excretion rates were assessed as an index of endogenous NO formation. Plasma L-arginine levels were not different between control and cholesterol-fed rabbits, but they were elevated nearly threefold in rabbits fed cholesterol + L-arginine. Plasma ADMA concentration increased about two-fold in hypercholesterolemia, but was unaffected by dietary L-arginine. Thus, dietary L-arginine elevated the plasma L-arginine/ADMA ratio above the normal level, and partly restored urinary nitrate excretion, which was decreased by hypercholesterolemia. We conclude that elevation of the L-arginine/ADMA ratio may at least partly explain the restored NO formation by exogenous L-arginine in hypercholesterolemia.
 ...
PMID:Elevated L-arginine/dimethylarginine ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits. 860 33

The incidence of erectile dysfunction increases with diabetes, hypertension, hypercholesterolaemia, cardiovascular disease and renal failure. All these conditions are associated with endothelial dysfunction. This review addresses the pathophysiology of erectile dysfunction with a special focus on new insights into nitric oxide (NO)-mediated pathways, oxidative stress and parallels to endothelial dysfunction. NO appears to be the key mediator promoting endothelium-derived vasodilation and penile erection. The possibility is discussed that elevated plasma concentrations of asymmetrical dimethylarginine (ADMA), an endogenous NO synthase inhibitor, may provide an additional pathomechanism for various forms of erectile dysfunction associated with cardiovascular risk factors and disease. Likewise, the role of endothelium-derived factors mediating NO-independent pathways is evaluated.
 ...
PMID:The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function. 1255 45

Despite significant progress in renal replacement therapy, the mortality from cardiovascular disease (CVD) in patients with chronic renal failure (CRF) is many times higher than in the general population. The traditional risk factors are frequently present in CRF patients. However, based upon conventional risk factor analysis, these factors do not fully explain the extraordinary increase in morbidity and mortality in CVD among patients with CRF. Accumulating evidence suggests that CRF is associated with impaired endothelial cell function. In recent years, the role of endothelial dysfunction (ED) and excessive oxidative stress (OS) in the development of CVD has been highlighted. ED is an early feature of vascular disease in different diseases such diabetes, hypertension, hypercholesterolemia, and coronary heart disease. The precise mechanism which induces ED is not clear. Several factors however, including OS-related accumulation of uremic toxins, hypertension and shear stress, dyslipidemia with cytotoxic lipoprotein species such as small, dense low-density lipoprotein (LDL) particles, competitive inhibition of endothelial nitric oxide (NO) by increased production by asymmetrical dimethylarginine (ADMA) are pathogenic. In addition, it is known that excessive OS causes ED. An overproduction of reactive oxygen species (ROS) may injure the endothelial cell membrane, inactivate NO, and cause oxidation of an essential cofactor of nitric oxide synthase (NOS). Recent studies have demonstrated that an impaired endothelium-dependent vasodilation and OS are closely related to each other in patients with CRF.
 ...
PMID:Endothelium-dependent vasodilation and oxidative stress in chronic renal failure: impact on cardiovascular disease. 1269 8

Plasma membranes are fluid structures and the maintenance of fluidity is a prerequisite for function, viability, growth and reproduction of cells. Membrane fluidity is the reciprocal of membrane microviscosity, which in turn is inversely proportional to rotational and lateral diffusion rates of membrane components. In the absence of constraints most lipids and unrestrained integral proteins freely diffuse in the plane of the membrane with high diffusion coefficients. The fluid mosaic model of plasma membrane structure is essentially still valid but this model is by its nature a macroscopic one. At present, attention is focused on molecular structural details of protein-lipid interactions and on the static and dynamic structure of membrane proteins. Highly potent new macroscopic and microscopic methods have been developed to measure translational diffusion of membrane lipids and proteins. The microscopic methods can reveal diffusion via encounters between labeled molecules. Fluorescence anisotropy measurements are the most widely used techniques in biological research. The use of different permeant and non-permeant fluorophores have contributed much to a better understanding of the changes in the ordered states and motional freedom of the membrane phospholipids in different cells during development, aging and physiological functions as well as in pathological conditions. The application of fluorophores with non-random distribution have shed light on the asymmetrical changes between the outer and inner domain of the lipid bilayer and on the dynamics of 'flip-flop' in signal transduction. Membrane fluidity was shown to have a decisive role in the efficiency of ligand binding, in the outcome of direct cell to cell contacts and in the modulation of the activity of membrane enzymes. Cell filtrability reflects whole cell viscosity that can not always be correlated with the fine changes in membrane fluidity. Cell viscosity depends inter alia on the size and shape of the cells as well as on membrane rigidity. In contrast to this, membrane fluidity is only dependent on the freedom of mobility of the membrane constituents. Increased release of free radicals and reactive oxygen specie (ROS) affect membrane fluidity, cellular Ca2+ homeostasis, induce lipid peroxidation and finally cell death. Investigation of membrane fluidity proved to be a useful and sensitive additional method to obtain a better insight into the mechanisms by which different compounds, drugs and contact with foreign surfaces are affecting cellular functions. The measurements of membrane fluidity may gain more widespread use for monitoring the safety and efficacy of these actions. During the last few years, changes in membrane fluidity of blood cells have been reported during development and aging and as a result of physiological cell functions. Membrane fluidity changes have been described in thrombocythaemia, hyperlipidaemia, hypercholesterolaemia, hypertension, diabetes mellitus, obesity, septic conditions and in allergic and burnt patients, in alcoholics, in Alzheimer's disease and in schizophrenia. A short summary is given on red cell membrane fluidity changes in a Hungarian triosephosphate isomerase (TPI)-deficient family, reflecting how the very subtle changes in membrane fluidity can help to establish underlying biological differences between the clinical phenotypes of a severe enzyme (TPI) deficiency caused by the defect of a single gene in two brothers one with and one without neurological symptoms.
 ...
PMID:Membrane fluidity of blood cells. 1465 48

This study examined the effects of a new phosphodiesterase type 5 inhibitor, DA-8159, on erectile function associated with hypercholesterolemia. First of all, in order to investigate whether chronic administration of DA-8159 prevents the development of erectile dysfunction associated with hypercholesterolemia, male SD rats were divided into four groups (normal control, hypercholesterolemic control, DA-8159 5 or 20 mg/kg/day). Over a 5-month period, the animals were fed a 2% cholesterol diet and administered DA-8159 orally once a day. After 5 months, the electrostimulation-induced penile erection and the vascular function using acetylcholine-induced vasodilation with endothelium-intact aortic rings were examined. Furthermore, the plasma lipid profiles, endothelin and N(G),N(G)-dimethylarginine (asymmetrical dimethylarginine, ADMA) concentrations were measured. In order to investigate the acute treatment effect of DA-8159 on the erectile function in an established hypercholesterolemic model, additional animals were given a 2% cholesterol diet for 5 months without DA-8159. At the end of 5 months, the rats were divided into three groups (hypercholesterolemic control, DA-8159 0.3 or 1 mg/kg). DA-8159 was administered intravenously 1 min prior to the intracavernous pressure (ICP) measurement. In a chronic treatment study, while the hypercholesterolemic control showed a significantly lower erectile function, vascular reactivity, and increased plasma cholesterol, endothelin and ADMA concentration, the chronic DA-8159 treatment clearly restored the erectile responses by electric stimulation, preserved the potential of thoracic aortic relaxation in a dose-dependent manner, and significantly decreased the plasma endothelin and ADMA concentrations. In an acute treatment study, DA-8159 induced a dose- and frequency-dependent increase in ICP. The ICP/BP ratio and the corresponding AUC values, and the detumescence time were also significantly increased compared to the hypercholesterolemic control. These results suggest that DA-8159 is beneficial for erectile dysfunction in a rat hypercholesterolemic model and provided a rationale for the potential use of DA-8159 for treating erectile dysfunction secondary to hypercholesterolemia.
 ...
PMID:The effect of DA-8159, a novel PDE5 inhibitor, on erectile function in the rat model of hypercholesterolemic erectile dysfunction. 1592 Apr 60