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)

Dexfenfluramine (Dex), an appetite suppressant and serotonin reuptake inhibitor, is associated with pulmonary vascular disease (PVD) in some patients. The variability might be related to undetermined genetic abnormalities interacting with factors such as gender, weight loss, and vascular injury. We, therefore, assessed the effect of Dex (5 mg. kg(-1). day(-1)) in female obese rats, designated JCR:LA-cp or cp/cp; in lean rats, designated (+/?); and in normal Sprague-Dawley (S-D) rats under control conditions or after endothelial injury induced by monocrotaline (60 mg/kg). Pulmonary arterial pressure, right ventricular hypertrophy, percent medial wall thickness of muscular arteries, and muscularization of peripheral arteries were assessed as indexes of PVD. Although Dex reduced weight gain in cp/cp and S-D rats (P < 0.05 for both), it did not cause PVD. Moreover, PVD in S-D rats after monocrotaline injection was paradoxically ameliorated by Dex (P < 0.05) despite induction of pulmonary artery elastase (P < 0.05), which we showed is critical in inducing experimental PVD. Thus it is possible that Dex is concomitantly offsetting the sequelae of elastase activity.
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PMID:Dexfenfluramine protects against pulmonary hypertension in rats. 1238 65

Hypertensive pulmonary vascular disease is characterized by abnormal proliferation of vascular endothelial and smooth muscle cells, leading to occlusion of pulmonary arterioles, pulmonary hypertension, right ventricular failure, and death. Compounds with antiproliferative effects on vascular endothelial and smooth muscle cells, such as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, may prevent the development of experimental hypertensive pulmonary vascular disease. Pneumonectomized rats injected with monocrotaline at 7 days develop severe hypertensive pulmonary vascular disease with neointimal formation. Rats were randomized to receive either vehicle or treatment with the HMG-CoA reductase inhibitor simvastatin (2 mg/kg per day). By Day 35, rats that received vehicle had higher mean pulmonary arterial pressures (53 +/- 2 mm Hg) and right ventricular hypertrophy (right ventricle/[left ventricle plus septum] [RV/LV+S] = 0.78 +/- 0.09) than rats in Group PMS5-35 that received simvastatin from Day 5 to 35 (mean pulmonary arterial pressure = 27 +/- 3 mm Hg, RV/LV+S = 0.34 +/- 0.08; p < or = 0.001). Pulmonary vascular remodeling with neointimal formation consisting of vascular smooth muscle cells was more severe in vehicle-treated rats (vascular occlusion score, 1.98 +/- 0.02) than in Group PMS5-35 (vascular occlusion score, 0.59 +/- 0.46; p < 0.001). In addition, lung endothelial nitric oxide synthase gene expression was decreased in vehicle-treated animals but was restored toward normal levels in simvastatin-treated animals. Simvastatin attenuates monocrotaline-induced pulmonary vascular remodeling with neointimal formation, pulmonary arterial hypertension, and right ventricular hypertrophy in rats.
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PMID:Simvastatin attenuates smooth muscle neointimal proliferation and pulmonary hypertension in rats. 1242 39

The goal of antihypertensive therapy is to provide effective treatment that can be sustained lifelong, while lowering elevated blood pressure and preventing hypertensive end-organ damage and mortality. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists (AIIAs) control blood pressure as well as other available classes of antihypertensive drugs. The ACE inhibitors have been demonstrated to reduce the incidence of stroke, reverse left ventricular hypertrophy, and improve congestive heart failure symptomatology and mortality to a similar degree as diuretics and beta-adrenergic blockers. ACE inhibitors reduce postmyocardial infarction recurrence, improve congestive heart failure symptomatology and mortality, and slow the progression of glomerular renal disease. The AIIAs reverse left ventricular hypertrophy. Several of these agents have been shown to improve congestive heart failure symptomology and mortality, to reduce the occurrence of early atherosclerotic vascular disease, and to slow the progression of renal failure in type 2 diabetes mellitus nephropathy. One AIIA has reduced the incidence of end-stage renal disease in non-insulin-dependence diabetes mellitus nephropathy over 3 years. Ideally, antihypertensive therapy should maintain or improve the patients quality of life without creating side effects or adverse laboratory effects. Among the available nine classes of antihypertensive drugs, ACE inhibitors and the AIIAs come close to meeting the description of an ideal drug. AIIAs and ACE inhibitors, two classes of antihypertensive drugs that reduce the activity of the renin-angiotensin II system, should be among the preferred first-step drugs for the treatment of hypertension.
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PMID:Drugs that interrupt the renin-angiotensin system should be among the preferred initial drugs to treat hypertension. 1267 27

Cardiovascular disease accounts for more than 50% of end-stage renal disease (ESRD) deaths. The reported cardiovascular death rates in patients receiving dialysis are substantially higher than in the general population. Cardiovascular mortality in ESRD is particularly high after acute myocardial infarction, but it is also elevated in ESRD patients with other forms of atherosclerotic vascular disease (eg, chronic coronary artery disease, strokes, transient ischemic attacks, and peripheral arterial disease). Left ventricular hypertrophy and dilation are associated with increased cardiovascular mortality, as is congestive heart failure. One of the major reasons for such high cardiovascular mortality in ESRD is the large burden of cardiovascular disease present in patients with chronic artery disease before renal replacement therapy. These observations mandate not only aggressive diagnosis and treatment of cardiovascular disease in patients with ESRD, but also active screening, diagnosis, and treatment in those with chronic kidney disease before renal replacement therapy.
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PMID:Cardiovascular mortality in end-stage renal disease. 1269 21

Even with modern treatment, acromegaly is associated with a 2- to 3-fold increase in mortality, mainly from vascular disease, which is probably a result of the long exposure of tissues to excess GH before diagnosis and treatment. There is accumulating evidence that effective treatment to lower serum GH levels to less than 1-2 ng/ml (glucose suppressed or random, respectively) and normalize IGF-I improves long-term outcome and survival. In addition to recognized cardiovascular risk factors of hypertension, type 2 diabetes mellitus, and dyslipidemia, there is accumulating evidence of specific structural and functional changes in the heart in acromegaly. Along with endothelial dysfunction, these changes may contribute to the increased mortality in this disease. There are specific structural changes in the myocardium with increased myocyte size and interstitial fibrosis of both ventricles. Left ventricular hypertrophy is common even in young patients with short duration of disease. Some of these structural changes can be reversed by effective treatment. Functionally, the main consequence of these changes is impaired left ventricular diastolic function, particularly when exercising, such that exercise tolerance is reduced. Diastolic function improves with treatment, but the effect on exercise tolerance is more variable, and more longitudinal data are required to assess the benefits. What scant data there are on rhythm changes suggest an increase in complex ventricular arrhythmias, possibly as a result of the disordered left ventricular architecture. The functional consequences of these changes are unclear, but they may provide a useful early marker for the ventricular remodeling that occurs in the acromegalic heart. Endothelial dysfunction, especially flow-mediated dilatation, is an early marker of atherosclerosis, and limited data imply that this is impaired in active acromegaly and can be improved with treatment. Similarly, early arterial structural changes, such as thickened intima media layer, appear more common in acromegalics, and there are hints that this may diminish with effective treatment, although more studies are required for a definite conclusion on this topic. In conclusion, impaired cardiac and endothelial structure and function in acromegaly are risk factors for vascular mortality and should be regarded as legitimate therapeutic targets in the overall management of this condition.
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PMID:Cardiovascular function in acromegaly. 1278 99

An elevation in angiotensin II (Ang II) levels is a common occurrence in a diverse number of cardiovascular diseases including hypertension, hypercholesterolaemia, atherosclerotic coronary artery disease, left ventricular hypertrophy (LVH), heart failure and diabetes. An important effect of Ang II is activation of the NAD(P)H oxidase, a major source of reactive oxygen species (ROS) production by vascular cells. This increase in cellular ROS contributes to the pathogenesis of vascular disease by altering endothelial cell function, enhancing smooth muscle cell growth and proliferation, stimulating inflammatory proteins, including macrophage chemoattractant agents, growth factors and cytokines, and modulating matrix remodelling. Studies of genetically-altered mice have unequivocally shown that activation of the NAD(P)H oxidase by Ang II contributes to hypertension, LVH and atherosclerosis. Furthermore, increasing evidence suggest that the NAD(P)H oxidase contributes to human disease, suggesting that it is a potential target for future therapeutic intervention.
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PMID:Interactions of angiotensin II with NAD(P)H oxidase, oxidant stress and cardiovascular disease. 1280 86

Clinical and epidemiologic data have demonstrated that microalbuminuria (MA) may legitimately be an integrated marker of cardiovascular risk in nondiabetic hypertensive patients. The relation of augmented urinary albumin excretion rate (UAER) with the other surrogates of the atherosclerotic process, such as carotid artery intima-media thickness, large artery elasticity, and left ventricular hypertrophy gives further support to this view. Available evidence so far indicate that MA possibly reflects a state of increased renal endothelial permeability and may be an easily measured marker of a rather diffuse endothelial dysfunction, low-grade inflammation, and vascular disease burden. Whether management of hypertensive populations may be improved by UAER monitoring and whether the reduction of UAER can decrease cardiovascular morbidity and mortality remains to be determined in the future.
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PMID:Inter-relationships of microalbuminuria with the other surrogates of the atherosclerotic cardiovascular disease in hypertensive subjects. 1511 Sep 9

Low-salt diets have potential for prevention and treatment of hypertension, and may also reduce risk for stroke, left ventricular hypertrophy, osteoporosis, renal stones, asthma, cataract, gastric pathology, and possibly even senile dementia. Nonetheless, the fact that salt restriction evokes certain counter-regulatory metabolic responses-- increased production of renin and angiotensin II, as well as increased sympathetic activity--that are potentially inimical to vascular health, has suggested to some observers that salt restriction might not be of unalloyed benefit, and might in fact be contraindicated in some "salt-resistant" subjects. Current epidemiology indicates that lower-salt diets tend to reduce coronary risk quite markedly in obese subjects, whereas the impact of such diets on leaner subjects (who are less likely to be salt sensitive) is equivocal--seemingly consistent with the possibility that salt restriction can exert countervailing effects on vascular health. There is considerable evidence that sodium chloride, rather than sodium per se, is responsible for the known adverse effects of dietary salt. Other non-halide sodium salts, such as sodium citrate or bicarbonate, do not raise plasma volume, increase blood pressure, boost urinary calcium loss, or promote stroke in stroke-prone rats. Nonetheless, these compounds have been shown to blunt the impact of salt restriction on renin, angiotensin II, and sympathetic activity in humans. This may rationalize limited clinical evidence that organic sodium salts can decrease blood pressure in salt-restricted hypertensives. Furthermore, organic sodium salts have an alkalinizing metabolic impact favorable to bone health. These considerations suggest that restricting dietary salt to the extent feasible, while encouraging consumption of organic sodium salts in mineral waters, soft drinks, or other nutraceuticals--preferably in conjunction with organic potassium salts and taurine--may represent a superior strategy for controlling blood pressure, promoting vascular health, and preserving bone density. Further clinical studies should determine whether a moderately salt-restricted diet supplemented with organic sodium salts has a better and more uniform impact on hypertension than salt restriction alone, while rodent studies should examine the comparative impact of these regimens on rodents prone to vascular disease.
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PMID:Should we restrict chloride rather than sodium? 1519 67

Bradykinin is an important modulator of endothelial cell function and has also a powerful cardioprotective effect. Here we report that treatment of severely pulmonary hypertensive rats (that recapitulate several of the physiological and pathological characteristics of the human pulmonary vascular disease, including dramatic right ventricular hypertrophy, pericardial effusion and death) with a newly synthesized long-acting bradykinin B2 receptor agonist B9972 caused reduction of the pulmonary artery pressure (PAP=51+/-2.0 versus 68+/-2.8 of untreated animals) and of right ventricular hypertrophy (Rv/Lv+S=0.55+/-0.02 versus 0.73+/-0.03 of untreated rats) and activation of Akt. Long-term stimulation with B9972 in our animal model of SPH resulted in decreased expression of the B2 receptor in lung vasculature. Treatment with B9972 decreased the number of plexiform lesions in the lungs by inducing cell apoptosis in the obliterated vessels and by restoring caveolin-1 expression. B9972 also promoted eNOS activation. In vitro B9972 caused activation of caspase-3 as well as Erk and induction of prostacyclin production in rat pulmonary microvascular EC. Taken together our data suggest that a stable bradykinin B2 agonist B9972 demonstrates the capacity to reduce severe pulmonary hypertension, right ventricular hypertrophy and induce apoptosis of hyperproliferative cells in pre-capillary pulmonary arterioles.
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PMID:Treatment of severe pulmonary hypertension: a bradykinin receptor 2 agonist B9972 causes reduction of pulmonary artery pressure and right ventricular hypertrophy. 1587 94

A 2-year-old morbidly obese boy presented with early manifestation of vascular disease associated with several obesity-related features of the metabolic syndrome due to massive overfeeding. Ultrasound of the carotid arteries showed significant thickening of the intima media, perfusion magnetic resonance spectroscopy indicated cerebral microcirculation disturbance, and echocardiography revealed left ventricular hypertrophy. Thorough assessment of morbidly obese children seems to be of importance from early childhood on. Studies evaluating the prevalence of obesity-related metabolic and vascular comorbidities in very young morbidly obese children are warranted.
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PMID:Early cerebrovascular disease in a 2-year-old with extreme obesity and complete metabolic syndrome due to feeding of excessively high amounts of energy. 1692 42


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