Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 67 year old woman developed acute renal failure with serum potassium 9.4 mmol/l requiring emergency dialysis after seven days of diarrhoea while taking an ACE inhibitor for vascular disease. Review of the literature, the British National Formulary, and the patient information leaflets for each of the 11 ACE inhibitors currently marketed in the UK suggests that this potentially life threatening complication of ACE inhibition is not yet widely recognised.
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PMID:Life threatening hyperkalaemia with diarrhoea during ACE inhibition. 1566 77

The family of potassium channel openers regroups drugs that share the property of activating adenosine triphosphate-sensitive potassium (K(ATP)) channels, metabolic sensors responsible for adjusting membrane potential-dependent functions to match cellular energetic demands. K(ATP) channels, widely represented in metabolically-active tissue, are heteromultimers composed of an inwardly rectifying potassium channel pore and a regulatory sulfonylurea receptor subunit, the site of action of potassium channel opening drugs that promote channel activity by antagonizing ATP-induced pore inhibition. The activity of K(ATP) channels is critical in the cardiovascular adaptive response to stress, maintenance of neuronal electrical stability, and hormonal homeostasis. Thereby, K(ATP) channel openers have a unique therapeutic spectrum, ranging from applications in myopreservation and vasodilatation in patients with heart or vascular disease to potential clinical use as bronchodilators, bladder relaxants, islet cell protector, antiepileptics and promoters of hair growth. While the current experience in practice with potassium channel openers remains limited, multitude of ongoing investigations aims at defining the benefit of this emerging family of therapeutics in diverse disease conditions associated with metabolic distress.
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PMID:K(ATP) channel therapeutics at the bedside. 1595 14

Induction of K(Ca)3.1 (IKCa) potassium channel plays an important role in vascular smooth muscle cell proliferation. Here, we report that the gene encoding K(Ca)3.1 (KCNN4) contains a functional repressor element 1-silencing transcription factor (REST or NRSF) binding site and is repressed by REST. Although not previously associated with vascular smooth muscle cells, REST is present and recruited to the KCNN4 gene in situ. Significantly, expression of REST declines when there is cellular proliferation, showing an inverse relationship with functional K(Ca)3.1. Downregulated REST and upregulated K(Ca)3.1 are also evident in smooth muscle cells of human neointimal hyperplasia grown in organ culture. Furthermore, inhibition of K(Ca)3.1 suppresses neointimal formation, and exogenous REST reduces the functional impact of K(Ca)3.1. Here, we show REST plays a previously unrecognized role as a switch regulating potassium channel expression and consequently the phenotype of vascular smooth muscle cells and human vascular disease.
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PMID:Downregulated REST transcription factor is a switch enabling critical potassium channel expression and cell proliferation. 1620 44

Sulphonylureas, such as glybenclamide and gliclazide, are classical blockers of ATP-dependent potassium channels (K(ATP)). Closure of K(ATP) channels in vascular smooth muscles by sulphonylureas would lead to membrane depolarization and vasoconstriction but this hypothesis has not been consistently proved in different types of vascular tissues. Our present study examined mouse vascular contractility changes induced by sulphonylureas using a wire myograph. The phenylephrine-precontracted aorta (n=6), super mesenteric arteries (n=10) and third-order mesenteric artery (n=10) from C57BL mice were relaxed by glybenclamide with IC(50) of 116+/-13.0, 61.8+/-5.5, and 41.4+/-1.3 microM, respectively. Gliclazide or U37883A (a vascular K(ATP) blocker structurally different from that of sulphonylureas) had similar vasorelaxant effects on mesenteric arteries with IC(50) of 14.8+/-1.5 microM (n=5) or 15.6+/-1.3 microM (n=9), respectively. The presence of Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME, 300 microM, n=8), apamin+charybdotoxin (n=4), or 1H-[1, 2, 4]-oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ) (10 microM, n=10) partially reduced vasorelaxant effect of glybenclamide on mesenteric arteries. Removal of endothelium (n=7) or precontraction with 100 mM [K(+)](o) (n=10) also significantly reduced vasorelaxant effect of glybenclamide on mesenteric arteries. The relaxation of mouse resistance arteries by K(ATP) channel blockers calls for further investigation into the selectivity and suitability of these drugs in treatment of different vascular disease.
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PMID:Sulphonylureas induced vasorelaxation of mouse arteries. 1794 9

Five types of oral antihyperglycemic drugs are currently approved for the treatment of diabetes: biguanides, sulfonylureas, meglitinides, glitazones and alpha-glucosidase inhibitors. We briefly review the cardiovascular effects of the most commonly used antidiabetic drugs in these groups in an attempt to improve knowledge and awareness regarding their influences and potential risks when treating patients with coronary artery disease (CAD). Regarding biguanides, gastrointestinal disturbances such as diarrhea are frequent, and the intestinal absorption of group B vitamins and folate is impaired during chronic therapy. This deficiency may lead to increased plasma homocysteine levels which, in turn, accelerate the progression of vascular disease due to adverse effects on platelets, clotting factors, and endothelium. The existence of a graded association between homocysteine levels and overall mortality in patients with CAD is well established. In addition, metformin may lead to lethal lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as heart failure or recent myocardial infarction. Sulfonylureas avoid ischemic preconditioning. During myocardial ischemia, they may prevent opening of the ATP-dependent potassium channels, impeding the necessary hyperpolarization that protects the cell by blocking calcium influx. Meglitinides may exert similar effects due to their analogous mechanism of action. During treatment with glitazones, edema has been reported in 5% of patients, and these drugs are contraindicated in diabetics with NYHA class III or IV cardiac status. The long-term effects of alpha-glucosidase inhibitors on morbidity and mortality rates and on diabetic micro- and macrovascular complications is still unknown. Combined sulfonylurea/metformin therapy reveals additive effects on mortality. Four points should be mentioned: (1) the five oral antidiabetic drug groups present proven or potential cardiac hazards; (2) these hazards are not mere 'side effects' but are deeply rooted in the drugs' mechanisms of action; (3) current data indicate that combined glibenclamide/metformin therapy seems to present a special risk and should be avoided in the long-term management of type 2 diabetics with proven CAD, and (4) Non-Insulin Antidiabetic Therapy in Diabetic Cardiac Patients 155 customized antihyperglycemic pharmacological approaches should be investigated for the optimal treatment of diabetic patients with heart disease. New possibilities are represented by incretin mimetic compounds, dipeptidyl peptidase (DPP)-4 inhibitors, inhaled insulin and eventually oral insulin.
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PMID:Non-insulin antidiabetic therapy in cardiac patients: current problems and future prospects. 1823 Sep 61

Calcium (Ca(2+)) is a highly versatile second messenger that controls vascular smooth muscle cell (VSMC) contraction, proliferation, and migration. By means of Ca(2+) permeable channels, Ca(2+) pumps and channels conducting other ions such as potassium and chloride, VSMC keep intracellular Ca(2+) levels under tight control. In healthy quiescent contractile VSMC, two important components of the Ca(2+) signaling pathways that regulate VSMC contraction are the plasma membrane voltage-operated Ca(2+) channel of the high voltage-activated type (L-type) and the sarcoplasmic reticulum Ca(2+) release channel, Ryanodine Receptor (RyR). Injury to the vessel wall is accompanied by VSMC phenotype switch from a contractile quiescent to a proliferative motile phenotype (synthetic phenotype) and by alteration of many components of VSMC Ca(2+) signaling pathways. Specifically, this switch that culminates in a VSMC phenotype reminiscent of a non-excitable cell is characterized by loss of L-type channels expression and increased expression of the low voltage-activated (T-type) Ca(2+) channels and the canonical transient receptor potential (TRPC) channels. The expression levels of intracellular Ca(2+) release channels, pumps and Ca(2+)-activated proteins are also altered: the proliferative VSMC lose the RyR3 and the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase isoform 2a pump and reciprocally regulate isoforms of the ca(2+)/calmodulin-dependent protein kinase II. This review focuses on the changes in expression of Ca(2+) signaling proteins associated with VSMC proliferation both in vitro and in vivo. The physiological implications of the altered expression of these Ca(2+) signaling molecules, their contribution to VSMC dysfunction during vascular disease and their potential as targets for drug therapy will be discussed.
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PMID:The non-excitable smooth muscle: calcium signaling and phenotypic switching during vascular disease. 1836 43

The content of total flavone in carthmus tinctorius L in Xinjiang was determined by ultraviolet spectrophotometry with scan from 200 to 400 nm where the maximum absorption wavelength was 267.00 nm. The contents of ten trace elements and constant elements in carthmus tinctorius L including potassium, sodium, calcium, magnesium, iron, chromium, nickel, manganese, copper and zinc were determined by flame atomic absorption spectrophotometry. The results showed that there were comparatively rich trace elements and high total flavone, among which are comparatively high calcium, magnesium, chromium, copper and zinc in carthmus tinctorius L. It provided useful data for discussing the relationship between the content of total flavone and the trace elements in carthmus tinctorius L, and for studing the relationship between the trace elements in carthmus tinctorius L and the cure for cardio-cerebral vascular disease.
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PMID:[Analysis and study of total flavone and trace element in carthmus tinctorius L]. 1842 59

Reduced-sodium, increased-potassium salt substitutes lower blood pressure but may also have direct effects on vascular structure and arterial function. This study aimed to test the effects of long-term salt substitution on indices of these outcomes. The China Salt Substitute Study was a randomized, controlled trial designed to establish the effects of salt substitute (65% sodium chloride, 25% potassium chloride, 10% magnesium sulfate) compared with regular salt (100% sodium chloride) on blood pressure among 600 high-risk individuals living in six rural areas in northern China over a 12-month intervention period. Data on central aortic blood pressure, aortic pressure augmentation (AUG), augmentation index (AIx), the differences of the peak of first and baseline waves (P(1)-P(0)) and pulse wave reflection time (RT) were collected at randomization and at the completion of follow-up in 187 participants using the Sphygmocor pulse wave analysis system. Mean baseline blood pressure was 150.1/91.4 mm Hg, mean age was 58.4 years, 41% were male and three quarters had a history of vascular disease. After 12 months of intervention, there were significant net reductions in peripheral (7.4 mm Hg, P=0.009) and central (6.9 mm Hg, P=0.011) systolic blood pressure levels and central pulse pressure (4.5 mm Hg, P=0.012) and correspondingly there was a significant net reduction in P(1)-P(0) (3.0 mm Hg, P=0.007), borderline significant net reduction in AUG (1.5 mm Hg, P=0.074) and significant net increase in RT (2.59 ms, P=0.001). There were no detectable reductions in peripheral (2.8 mm Hg, P=0.14) or central (2.4 mm Hg, P=0.13) diastolic blood pressure levels or AIx (0.06%, P=0.96). In conclusion, over the 12-month study period the salt substitute significantly reduced not only peripheral and central systolic blood pressure but also reduced arterial stiffness.
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PMID:Effects of salt substitute on pulse wave analysis among individuals at high cardiovascular risk in rural China: a randomized controlled trial. 1926 99

Magnesium (Mg) is the main intracellular divalent cation, and under basal conditions the small intestine absorbs 30-50% of its intake. Normal serum Mg ranges between 1.7-2.3 mg/dl (0.75-0.95 mmol/l), at any age. Even though eighty percent of serum Mg is filtered at the glomerulus, only 3% of it is finally excreted in the urine. Altered magnesium balance can be found in diabetes mellitus, chronic renal failure, nephrolithiasis, osteoporosis, aplastic osteopathy, and heart and vascular disease. Three physiopathologic mechanisms can induce Mg deficiency: reduced intestinal absorption, increased urinary losses, or intracellular shift of this cation. Intravenous or oral Mg repletion is the main treatment, and potassium-sparing diuretics may also induce renal Mg saving. Because the kidney has a very large capacity for Mg excretion, hypermagnesemia usually occurs in the setting of renal insufficiency and excessive Mg intake. Body excretion of Mg can be enhanced by use of saline diuresis, furosemide, or dialysis depending on the clinical situation.
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PMID:Magnesium metabolism in health and disease. 1927 87

The neurovascular unit (NVU) comprises cerebral blood vessels and surrounding astrocytes, neurons, perivascular microglia and pericytes. Astrocytes associated with the NVU are responsible for maintaining cerebral blood flow and ionic and osmotic balances in the brain. A significant proportion of individuals with Alzheimer's disease (AD) have vascular amyloid deposits (cerebral amyloid angiopathy, CAA) that contribute to the heterogeneous nature of the disease. To determine whether NVU astrocytes are affected by the accumulation of amyloid at cerebral blood vessels we examined astrocytic markers in four transgenic mouse models of amyloid deposition. These mouse models represent mild CAA, moderate CAA with disease progression to tau pathology and neuron loss, severe CAA and severe CAA with disease progression to tau pathology and neuron loss. We found that CAA and disease progression both resulted in distinct NVU astrocytic changes. CAA causes a loss of apparent glial fibrillary acidic protein (GFAP)-positive astrocytic end-feet and loss of water channels (aquaporin 4) localized to astrocytic end feet. The potassium channels Kir4.1, an inward rectifying potassium channel, and BK, a calcium-sensitive large-conductance potassium channel, were also lost. The anchoring protein, dystrophin 1, is common to these channels and was reduced in association with CAA. Disease progression was associated with a phenotypic switch in astrocytes indicated by a loss of GFAP-positive cells and a gain of S100 beta-positive cells. Aquaporin 4, Kir4.1 and dystrophin 1 were also reduced in autopsied brain tissue from individuals with AD that also display moderate and severe CAA. Together, these data suggest that damage to the neurovascular unit may be a factor in the pathogenesis of Alzheimer's disease.
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PMID:Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease. 1935 89


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