Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies suggest that 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, can have direct effects on blood vessels beyond their cholesterol-lowering effects. We investigated the effects of atorvastatin on the functional and structural properties of blood-brain barrier (BBB) and the activity of astrocytes during the N(omega)-nitro-L-arginine methyl ester (L-NAME) hypertension followed by angiotensin (ANG) II. We found that decreases in concentration of serum catalase and plasma nitric oxide (NO) induced by L-NAME were significantly ameliorated by atorvastatin, whereas L-NAME-induced serum malondialdehyde and cholesterol concentration increases were significantly reduced by atorvastatin. The content of Evans blue (EB) dye significantly increased in cerebellum, left cerebral cortex and diencephalon regions but atorvastatin markedly reduced the increased BBB permeability to EB in the brain regions of animals treated with L-NAME and L-NAME plus ANG II. Brain vessels of L-NAME-treated animals showed a considerable loss of immunoreactivity of tight junction proteins, zonula occludens (ZO)-1 and occludin. Immunoreactivity for ZO-1 and occludin increased in animals treated with atorvastatin and L-NAME plus atorvastatin. Glial fibrillary acidic protein (GFAP) immunoreactivity was seen in few astrocytes in the brain sections of L-NAME, but immunoreactivity for GFAP increased in L-NAME plus atorvastatin-treated animals. We suggest that long-term L-NAME treatment may affect BBB permeability through disruption of tight junction proteins, at least partly, via decreased NO concentration and increased oxidant capacity; the improvement of BBB integrity and astrocytic activity would be more closely associated with the action of atorvastatin favoring the increase in anti-oxidant capacity and expression of tight junction proteins and GFAP.
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PMID:Effects of atorvastatin on blood-brain barrier permeability during L-NAME hypertension followed by angiotensin-II in rats. 1585 90

Cardiovascular disease (CVD) is the leading cause of death worldwide. Many serious cardiovascular (CV) events occur in individuals with no prior manifestation of the disease, and often result in death. Awareness of the contributions of various risk factors to the occurrence of CVD is growing. Asymptomatic individuals with multiple risk factors at low or moderate levels can be at greater risk for CVD than those with a single risk factor at a high level. Dyslipidemia and hypertension are two risk factors that commonly coexist and are modifiable through lifestyle changes and/or medications. Recent trials with hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated that aggressive cholesterol-lowering therapy in patients without known atherosclerotic disease, but at high risk for CVD with relatively normal low-density lipoprotein cholesterol (LDL-C) levels (< 130 mg/dL), can significantly reduce the number of coronary events experienced by these patients. This subset of at-risk patients is better served by this approach than by treatment solely based on degree of dyslipidemia.
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PMID:Primary prevention trials: lessons learned about treating high-risk patients with dyslipidemia without known cardiovascular disease. 1600 78

About 90% of cases of hemorrhagic uremic syndrome (HUS) occur in early childhood and most frequently are preceded by bloody diarrhea due to shiga-like toxin (SLT) producing Escherichia coli. We report a case of a newborn girl presenting with bloody diarrhea on her 7th day of life. Acute renal failure, severe arterial hypertension and hemolytic anemia were detected and prompt peritoneal dialysis and antihypertensive therapy were required. The girl had several episodes of seizures, necessitating intravenous phenobarbital. Transfontanel ultrasonography 48 h after disease onset was normal, whereas, MRI investigation 10 days later revealed severe ischemic lesions with beginning cystic encephalopathy. Renal function recovered and only very moderate tubular dysfunction remained. Serum analysis of factor H, von Willebrand factor protease, homocystinemia, proteins C and S, and antithrombin III were all normal. Mutation analysis of factor V Leiden, factor II, and methyltetrahydrofolate-reductase were normal. E. coli 0157:H7 and SLT 2 were detected in the stool. SLT 2 was also found in the mother's stool. This is the first report of mother-to-child transmission of SLT-producing E. coli.
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PMID:Neonatal hemolytic uremic syndrome after mother-to-child transmission of Escherichia coli O157. 1601 May 98

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are often prescribed in association with antihypertensive agents, including calcium antagonists. Simvastatin is an HMG-CoA reductase inhibitor that is metabolized by the cytochrome P450 (CYP) 3A4. The calcium antagonist amlodipine is also metabolized by CYP3A4. The purpose of this study was to investigate drug interactions between amlodipine and simvastatin. Eight patients with hypercholesterolemia and hypertension were enrolled. They were given 4 weeks of oral simvastatin (5 mg/day), followed by 4 weeks of oral amlodipine (5 mg/day) co-administered with simvastatin (5 mg/day). Combined treatment with simvastatin and amlodipine increased the peak concentration (C(max)) of HMG-CoA reductase inhibitors from 9.6 +/- 3.7 ng/ml to 13.7 +/- 4.7 ng/ml (p < 0.05) and the area under the concentration-time curve (AUC) from 34.3 +/- 16.5 ng h/ml to 43.9 +/- 16.6 ng h/ml (p < 0.05) without affecting the cholesterol-lowering effect of simvastatin. This study is the first to determine prospectively the pharmacokinetic and pharmacodynamic interaction between amlodipine and simvastatin.
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PMID:Interaction between amlodipine and simvastatin in patients with hypercholesterolemia and hypertension. 1609 65

Doctors prescribe patients more and more medications. This predominantly affects elderly people. Polypharmacy is more and more frequent and predominantly affects elderly people. It may lead to many harmful and virtually life threatening drug interactions. There is pressing need to investigate new remedies, which would be applied in many different and coexisting medical conditions. It is vital particularly in case of elderly people who usually suffer from many different diseases which have numerous common pathogenetic pathways. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are a widely prescribed drug class for treatment of dyslipidemias and their complications such as coronary artery disease, stroke and peripheral arteriosclerosis. Now, there is accumulating evidence that statins also have beneficial pleiotropic effects that may make them useful in treatment of such diseases as dementia, osteoporosis, some forms of cancer, diabetes mellitus and its microangiopathic complications, hypertension and prevent deep vein thrombosis. Should we call statins "21st century aspirin?" This paper reviews recent data concerning the possibility of using statins in new indications; particularly in dementia (including Alzheimer's disease), osteoporosis, cardiovascular accidents and some forms of neoplasms.
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PMID:[Statins--"21st century aspirin"?]. 1619 42

Hypertension is known to be associated with an oxidative stress resulting from an imbalance of antioxidant defense mechanisms in various tissues. The purpose of this study was to investigate the relationship between the increase of arterial blood pressure, measured during the gradual development of experimental hypertension in deoxycorticosterone (DOCA)-salt-treated rats, and an early imbalance of liver antioxidant status. The levels of liver oxidant/antioxidant markers and iron were studied during the induction of hypertension in 3-, 6-, and 8-wk DOCA-salt-treated Sprague-Dawley rats. Hepatic antioxidant defenses were decreased as early as 3 wk of hypertensive treatment: the decrease of peroxidase-reductase-transferase and catalase activities was associated with a significant increase of thiobarbituric acid reactive substances (TBARS) levels. Liver oxidative stress increased until 6 wk and remained stable at 8 wk of DOCA-salt treatment. Concurrently, liver iron levels were increased at 6 wk and returned to normal values after 8 wk of hypertensive treatment. Iron seems to be an inductor of liver oxidative stress and responsible for the persistent oxidative stress, most likely through secondary free-radical release. Thus, our data (1) confirm that hypertension in DOCA-salt-treated rats might be a free-radical-dependent disease where hepatic oxidant/antioxidant imbalance is obviously involved from the beginning of blood pressure elevation and (2) suggest that the use of suitable iron chelators might reverse liver oxidative stress associated with the increase of blood pressure.
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PMID:Evolution of liver antioxidant status and iron implication during the development of deoxycorticosterone-saline hypertension in rats. 1628 82

Myopathy and rhabdomyolysis are rare adverse effects of treatment with hydroxymethylglutaryl-coA reductase inhibitors. The risk of adverse effects is increased with the concomitant use of statin and specific drugs that can induce myopathy, in patients with liver and renal function impairment, hypothyroidism and diabetes mellitus. The clinical picture of rhabdymyolysis with acute renal failure caused by the use of simvastatin in a 54-year-old patient with diabetes mellitus and hypertension is described.
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PMID:[Rhabdomyolysis as a side effect of simvastatin treatment]. 1633 40

Aldosterone is the principal endogenous mineralocorticoid in humans and regulates salt and water homeostasis. Cortisol, the major glucocorticoid, has high affinity for the mineralocorticoid receptor; however, 11beta-hydroxysteroid dehydrogenase type 2 converts cortisol to the inactive steroid cortisone in aldosterone target cells of the kidney, thus limiting the mineralocorticoid action of cortisol. Deoxycorticosterone (DOC) binds to the mineralocorticocoid receptor with high affinity and circulates at concentrations comparable to aldosterone. Severe DOC excess as is seen in 17alpha- and 11beta-hydroxylase deficiencies causes hypertension, and moderate DOC overproduction in late pregnancy is associated with hypertension. Here, we demonstrate that DOC is inactivated by the 20-ketosteroid reductase activity of the human AKR1C3 isozyme. Immunohistochemical analyses demonstrate that AKR1C3 is expressed in the mineralocorticoid-responsive epithelial cells of the renal cortical and medullary collecting ducts, as well as the colon. Our findings suggest that AKR1C3 protects the mineralocorticoid receptor from activation by DOC in mineralocorticoid target cells of the kidney and colon, analogous to cortisol inactivation by 11beta-hydroxysteroid dehydrogenase type 2.
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PMID:Deoxycorticosterone inactivation by AKR1C3 in human mineralocorticoid target tissues. 1633 83

The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was the first trial of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) to assess the benefits of lipid lowering in the primary prevention of coronary heart disease (CHD) in patients with hypertension who were not deemed to have dyslipidemia by conventional measures. A total of 19,342 patients with hypertension and > or =3 cardiovascular risk factors, but without CHD, were enrolled in ASCOT. Of these, 10,305 patients with a serum cholesterol level of < or =250 mg/dL (< or =6.5 mmol/L) were randomized to either atorvastatin (10 mg/day) or placebo in the ASCOT lipid-lowering arm (ASCOT-LLA). Follow-up was planned for an average of 5 years. The ASCOT-LLA was stopped after 3.3 years owing to the superiority of atorvastatin 10 mg over placebo in reducing the primary end point of nonfatal myocardial infarction (MI) and fatal CHD. Patients receiving atorvastatin experienced a significant reduction in total cholesterol (50 mg/dL [1.3 mmol/L]) and low-density lipoprotein cholesterol (46 mg/dL [1.2 mmol/L]) levels after 1 year compared with those who received placebo. Cholesterol lowering with atorvastatin was associated with a highly significant reduction in the primary end point of nonfatal MI and fatal CHD (36%, P = 0.0005). The observed benefit was consistent across the secondary end points and the 18 prespecified subgroups. The ASCOT-LLA findings have influenced lipid-lowering guidelines and support the concept that treatment strategies to reduce cardiovascular disease should be based on the assessment of all cardiovascular risk factors, rather than on numerical thresholds of individual risk factors, to determine treatment strategies.
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PMID:Lipid-lowering therapy and the patient with multiple risk factors: what have we learned from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)? 1635 1

Atherogenic dyslipidemia is one of the major components of the metabolic syndrome, a complex cluster of several risk factors within a single patient that according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III includes at least 3 of the following: large waist circumference, elevated triglyceride levels, low levels of high-density lipoprotein cholesterol (HDL-C), hypertension, and elevated fasting glucose levels, which are directly related to the incidence of coronary heart disease. Atherogenic dyslipidemia clinically presents as elevated serum triglyceride levels, increased levels of small dense low-density lipoprotein (sdLDL) particles, and decreased levels of HDL-C. An important component of atherogenic dyslipidemia is central obesity, which is defined as increased waist circumference and has recently been identified as a chief predictor of the metabolic syndrome in certain patients. Another recent study found that both body mass index and waist circumference were highly predictive of eventual development of the metabolic syndrome. Because atherogenic dyslipidemia usually precedes the clinical manifestation of the metabolic syndrome, strategies to treat it are the focus of pharmacologic intervention. For example, the 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors, commonly known as statins, benefit hypercholesterolemic patients who have atherogenic dyslipidemia that is associated with the metabolic syndrome. Pioglitazone, an antidiabetic agent that acts primarily by decreasing insulin resistance, improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Pioglitazone improves glycemic control while reducing circulating insulin levels. The investigational agent, rimonabant--a centrally and peripherally acting, selective cannabinoid type-1 receptor blocker--is the first therapy developed for managing several cardiovascular risk factors at one time. Rimonabant has shown promise in attacking atherogenic dyslipidemia from several vantage points by affecting glucose, HDL-C, triglycerides, and waist circumference in patients who are prone to atherogenic dyslipidemia.
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PMID:The metabolic basis of atherogenic dyslipidemia. 1647 58


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