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)

Acetylcholine-induced vasodilatation is impaired in animal models of insulin-dependent diabetes mellitus (IDDM), and may result from altered nitric oxide synthesis or release. The response to intraluminal flow, a more physiologically relevant stimulus for nitric oxide release, is unknown. This study examined flow-induced responses in isolated resistance arteries from male Sprague-Dawley control and streptozotocin-diabetic (45 mg/kg i.v., 4 week duration) rats. Mesenteric arteries (4-5th order) were dissected and cannulated on a pressure myograph (mean internal diameter +/- SEM at 40 mmHg, control 223 +/- 8, n = 9 vs diabetic 239 +/- 12 microm, n = 8, NS). Arteries were preconstricted with noradrenaline (1 micromol/l) and intraluminal pressure raised and maintained at 80 mmHg. Luminal flow was raised in incremental steps (0-1.27 microl/s). Arteries from control animals dilated to flow while arteries from diabetic animals constricted (% change in internal diameter +/- SEM at 0.79 microl/s: control 13.46 +/- 6.52, n = 9 vs diabetic -7.44 +/- 3.38%, n = 8; p < 0.005). Incubation with N(omega)-nitro-L-arginine methyl ester (0.1 mmol/l) abolished flow responses in arteries from controls but not from diabetic rats. In conclusion, impaired flow-induced nitric oxide-mediated vasodilatation may contribute to vascular disease in IDDM.
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PMID:Flow-induced dilatation in isolated resistance arteries from control and streptozotocin-diabetic rats. 949 27

An infant girl, born small for gestational age, with abnormal single creases on the fifth digits, subsequent severe developmental delay, hypertelorism, bilateral equinovalgus deformities, grade IV genitourinary reflux and mild right hydronephrosis, was found to have an inverted duplication of the short arm of chromosome 16 [46,XX; inv dup (16) (p 13.3-->p 11.2]. The cardiac anomalies included a large perimembranous ventricular septal defect (VSD) and a moderate-sized atrial septal defect (ASD). Cardiac catheterization at 6 months of age revealed systemic level pulmonary artery pressure, bilateral pulmonary venous desaturation, and in room air a pulmonary/systemic blood flow ratio (Qp/Qs) of 0.8:1.0, which did not change significantly with administration of oxygen and nitric oxide. To our knowledge, this is the first description of early nonreactive pulmonary vascular disease in a patient with duplication 16p and a large VSD.
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PMID:Pulmonary hypertension and trisomy 16. 956 17

Vascular disease is the leading cause of morbidity, disability and death in patients with noninsulin-dependent diabetes mellitus. Abnormalities in endothelium-derived nitric oxide (NO) have been demonstrated to be involved in the pathogenesis of vascular disease. By measuring hemodynamic responses to a NO synthase agonist or antagonist, previous studies have shown the presence of NO deficiency in patients with noninsulin-dependent diabetes mellitus, a method of assessing bioactive NO formation. However, direct biochemical evidence that this is the case, has not been produced. In vivo NO is metabolized into nitrate, an end breakdown product of NO, which can be used as an index of endogenous NO formation. To investigate further whether decreased basal synthesis of NO may be a major cause of endothelium-mediated vascular dysfunction in patients with noninsulin-dependent diabetes mellitus, the plasma nitrite/nitrate levels of 15 patients were examined and compared with 13 normal controls. The results showed that in basal conditions plasma nitrite/nitrate levels were not reduced in diabetic patients compared with normal controls (37.3 +/- 14.7 versus 29.4 +/- 8.6 mumol/l). It was concluded that in noninsulin-dependent diabetes mellitus patients, endothelium-derived basal NO formation is not impaired. This study, taken with previous observations, suggests that factors other than diminished basal NO production, such as reduced bioavailability of NO probably due to the augmented production of superoxide anion with subsequently increased inactivation of NO, contribute to the high incidence of vascular disease in patients with noninsulin-dependent diabetes mellitus.
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PMID:Basal nitric oxide production is not reduced in patients with noninsulin-dependent diabetes mellitus. 957 3

Normal menstruation involves the breakdown, remodelling and repair of the functional endometrial layers. Endometrial destruction and regeneration are largely controlled local factors, that are dependent on the levels of estradiol and progesterone. Prostaglandins and endothelins appear to be powerful vasoactive substances in the control of menstrual blood loss. The tissue endothelin concentration may interact with relaxing factors, such as nitric oxide, prolonging or increasing menstrual blood loss. Disturbances of menstrual bleeding and dysmenorrhea are a major medical problem not only for women but also for their families and health services. Management of dysfunctional uterine bleeding is determined by the needs of the patient: oral contraceptives are used for women of reproductive age with ovulatory uterine bleeding episodes who also require contraception; they have a strong progestogenic effect that is evident as early as the first week of pill intake. In the perimenopausal patient, dysfunctional uterine bleeding may be treated by cyclic progestins with or without conjugated equine estrogens; oral contraceptives can also be used in non-smokers who have no evidence of vascular disease. Dysmenorrhea is defined as a complaint of pain experienced during or immediately before menstruation. In the pathogenesis of dysmenorrhea, prostaglandins and arachinodonic acid metabolites play an important role, being elevated in women with dysmenorrhea. Oral contraceptives are very effective in the treatment of dysmenorrhea; they act mainly by reducing the levels of the prostaglandins and arachinodonic acid metabolites. For women reluctant to take oral contraceptives, non-steroidal anti-inflammatory drugs may be a better option.
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PMID:Dysfunctional uterine bleeding and dysmenorrhea. 967 78

A variety of signs and symptoms constituting the uraemic syndrome may be related to the retention and accumulation of uraemic toxins. Several identified (and yet unidentified) uraemic toxins of low molecular weight are removed at least in part by dialysis therapy resulting in marked improvement of multiple organ dysfunctions and clinical symptoms. However, many abnormalities persist due to the high protein binding of several uraemic toxins or their high molecular weight associated with inadequate dialysis clearance. Moreover, carbamoylation of amino acids and proteins in uraemia as well as metabolic acidosis contribute to the functional and metabolic abnormalities of the uraemic state. Uraemia interferes with the function of polymor-phonuclear leukocytes by deranging their cellular biochemistry and biology. P-cresol and several newly identified granulocyte inhibitory proteins are responsible for reduced chemotaxis, oxidative activity, intracellular killing of bacteria, and glucose consumption by polymorphonuclear leukocytes. Hyperhomocysteinaemia is an independent risk factor for vascular disease in end-stage renal disease patients. Uraemic toxins interfere with calcitriol synthesis and concentration or activity of the calcitriol receptor. Advanced glycolysation end-products (AGEs) accumulate as a result of impaired renal excretion. AGE peptides may represent a modern-day version of "middle molecule" toxicity or uraemia. Of potential clinical importance are pentosidine-, imidazolone- and carboxymethyllysine-modifications of beta 2-microglobulin with respect to the development of uraemia associated amyloidosis. Several uraemic toxins also affect nitric oxide pathway. Particularly, dimethyl-L-arginine (ADMA) is a potent inhibitor of nitric oxide synthesis. Parathyroid hormone satisfies the strict criteria of an uraemic toxin. Many uraemic symptoms can be attributed to the excess of parathyroid hormone in patients with chronic renal failure. Finally, recent investigations indicate, that one or more dialyzable uraemic toxin(s) suppress(es) appetite and may contribute to malnutrition in uraemia.
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PMID:Genesis of the uraemic syndrome: role of uraemic toxins. 978 69

Endothelial cells control the tone of the underlying vascular smooth muscle by secreting vasodilator substances (prostacyclin, nitric oxide and endothelium-derived hyperpolarizing factor). These vasodilator substances also contribute to the antithrombogenicity of the normal endothelium, and inhibit cellular growth. In coronary vascular disease, the ability of the endothelium to secrete vasodilator substances is reduced, while the propensity to release endothelium-derived contracting factors is increased. In particular, the reduced release of nitric oxide in response to aggregating platelets, thrombin and circulating catecholamines favours the occurrence of thrombosis and vasospasm, and plays a key role in the initiation of the atherosclerotic process. From the therapeutic point of view, the best available way to enhance the release of endothelium-derived nitric oxide and hyperpolarizing factor is to inhibit converting enzyme. This will protect endogenous bradykinin from breakdown and prolong its action on endothelial receptors.
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PMID:Endothelial dysfunction and inhibition of converting enzyme. 979 35

Diabetes mellitus is a complex disease characterised by chronic hyperglycaemia responsible for complications affecting the kidneys, eyes, peripheral nerves and micro- and macrovascular systems. Von Willebrand factor (vWf), a multimeric glycoprotein mainly synthesised by endothelial cells, is involved in platelet adhesion and aggregation and acts as the carrier of coagulation factor VIII in plasma. Increased levels of vWf, reflecting activation of or damage to endothelial cells, have been described in association with atherosclerosis and diabetes. vWf appears to be a predictive marker of diabetic nephropathy and neuropathy, although not of retinopathy, which suggests that endothelial dysfunction precedes the onset of diabetic microangiopathy. This dysfunction could be especially involved in the pathogenesis of renal abnormalities of diabetes. vWf is not a predictive marker of macroangiopathy when diabetes is associated with atherosclerotic risk factors. In the presence of chronic diabetic complications, vWf levels are not associated with any grade of retinopathy but increase with the severity of nephropathy and would appear to be a risk factor for macrovascular mortality in these patients. The endothelial dysfunction of diabetes can generate atherosclerotic lesions responsible for damage to the arterial wall, atheroma and formation of platelet microaggregates. Concomitant with high vWf levels, other possible mechanisms of endothelial damage include reduced synthesis or release of nitric oxide, hyperglycaemic pseudohypoxia and protein kinase-C activation, increased synthesis of proteins bearing advanced glycosylation end-products or transforming growth factor-beta (TGF-beta) activation of coagulation and inhibition of fibrinolysis. At present, it is not known whether high vWf levels are inherent to the physiopathology of diabetes, nor whether diabetes induces endothelial dysfunction through other pathways. However, since angiopathy resulting from endothelial dysfunction is the main cause of morbidity and mortality in diabetic patients, appropriate therapy is necessary to reduce these complications. Glycaemic control seems to be insufficient to normalise plasma vWf, whereas a decrease can be obtained by ingestion of diets rich in oleic acid or by treatment with statins. Inhibition of the binding of vWf to the GPlba receptor by synthetic peptides, aurin tricarboxylic acid or monoclonal antibodies has been proposed to prevent the thrombosis induced by high levels of plasma vWf. Thus, vWf probably represents an interesting target for the inhibition of thrombosis in diabetes.
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PMID:Von Willebrand factor in diabetic angiopathy. 980 43

1. Nitric oxide (NO) has important roles in physiological vasodilatation, cytotoxicity and vascular disease. Nitric oxide and prostacyclin (PGI2), both released from the endothelium, act synergistically to inhibit platelet aggregation and adhesion. These autacoids also inhibit the adhesion and migration of leucocytes and, in some arteries, they synergize in terms of vasodilation. 2. The development of atherosclerosis and hyperlipaemia per se is accompanied by impairment of endothelium-dependent vasodilation. 3. Atherosclerosis is associated with marked changes in the activity of isoforms of NO synthase (NOS) in the artery wall, including increased expression of the NOS2 (inducible) isoform in complex human lesions as well as in the neointima of experimental animal models. 4. Failure of NO release from the endothelium with normal physiological stimuli, which has been attributed to a defect in the operation of the endothelial NOS (NOS3), provides conditions propitious for leucocyte adhesion, vasospasm, thrombosis and, in addition, may promote increased proliferation of intimal cells. 5. Nitric oxide and superoxide anions generated by inflammatory cells in atherosclerosis react to form cytodestructive peroxynitrite radicals, potentially causing injury to the endothelium and myocytes, and this may be a factor in apoptosis of cells leading to plaque rupture. 6. We have been able to reverse these NO defects with therapeutic agents, including angiotensin-converting enzyme inhibitors, antagonists of platelet-activating factor and NO donor compounds, all offering promise in protecting against some manifestations of vascular disease.
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PMID:Nitric oxide in atherosclerosis: vascular protector or villain? 980 90

An imbalance between nitric oxide (NO) and superoxide is importantly involved in the pathogenesis of vascular disease. Inflammatory stimuli and risk factors contribute to these alterations. Calcium antagonists and angiotensin-converting enzyme inhibitors are commonly used cardiovascular drugs. To clarify the effect of felodipine and ramiprilat on the balance of these free radicals, we stimulated human aortic smooth muscle cells (HASCs) with cytokines (human interleukin-1beta, tumor necrosis factor-alpha, lipopolysaccharide, and/or interferon-gamma) or high glucose in the presence and absence of these compounds. Felodipine, but not ramiprilat, concentration-dependently inhibited cytokine-induced NO production and NO synthase (NOS) mRNA induction. The antioxidant N-acetylcysteine also inhibited cytokine-induced NO production and induction of inducible NOS mRNA. Moreover, felodipine inhibited cytokine-induced superoxide production both in the presence and absence of an NOS inhibitor, suggesting that it acted as a superoxide scavenger and not as an inhibitor of inducible NOS induction. High glucose treatment (22 mmol/L for 48 hours) also significantly increased superoxide production in HASCs, and this increase was inhibited in a concentration-dependent manner by felodipine but not by ramiprilat. These results suggest that felodipine may exert vascular protective effects by suppressing free radical generation in human smooth muscle cells during activation of inflammatory mechanisms and diabetic conditions.
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PMID:Felodipine inhibits free-radical production by cytokines and glucose in human smooth muscle cells. 985 65

Cardiovascular complications represent by far the most severe manifestations of diabetes mellitus. Treatment aimed at stopping progression of vascular lesions may fall short if initiated when the disease becomes clinically evident. Therefore, identification of the earliest vascular disfunctions may offer the best opportunity to interfere with pathogenic mechanisms and avoid progression of diabetic vasculopathy. In this report, we present a few mechanisms that alter hemodynamic and metabolic homeostasis in the course of diabetes mellitus. Endothelial function with special emphasis on nitric oxide and oxidative stress, advanced glycation end products, and the renin angiotensin system are briefly discussed. New pharmacological agents that may favorably influence these parameters are presently undergoing clinical trials. However, tight control of plasma glucose and cardiovascular risk factors represent the cornerstone of the treatment in diabetes to slow progression of vascular disease.
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PMID:Diabetes mellitus and vascular lesions. 986 65


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