Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calpain, a calcium-dependent, neutral cysteine-protease was purified from the erythrocyte cytosol of subjects having essential hypertension (HTN), sickle cell anaemia, (SCA), or kwashiorkor (KWA). Identical electrophoretic mobility on SDS-polyacrylamide gradient gel, sensitivity to micromolar amounts of Ca2+, absolute requirement for a reducing environment and a high susceptibility to inhibition by leupeptin and thiol-group modifying reagents confirm that calpain preparations from these erythrocytes are equivalent to calpain I. Whereas the extent of calpain activation of erythrocyte membrane Ca2(+)-pumping ATPase of normal subjects was almost equal to that due to calmodulin, calpain activation of the HTN and SCA pump was greater than activation by calmodulin. Like in normal membranes, exogenous calmodulin protected the Ca2(+)-pumping ATPase of these erythrocytes against calpainization; the degree of protection by calmodulin is least in SCA and HTN. Electrophoretic separation of erythrocyte membranes and the purified Ca2(+)-pumping ATPase of HTN, SCA and KWA subjects does not indicate the presence of fragments resulting from the proteolytic action of calpain.
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PMID:Comparative action of calpain on erythrocyte Ca2(+)-pumping ATPase in sickle cell anaemia, essential hypertension and kwashiorkor. 214 87

By inhibiting ACE, captopril blocks the conversion of AI or AII and augments the effects of bradykinin both in vitro and in vivo. In rats, dogs, and monkeys with 2-kidney renal hypertension, orally administered captopril rapidly and markedly reduces blood pressure; this antihypertensive effect apparently occurs via a renin-dependent mechanism; that is, the inhibition of ACE. In 1-kidney renal hypertension studies in rats and dogs, it was determined that oral doses of captopril markedly lowered blood pressure, but only after several days of dosing; the mechanism is thought to be non-renin dependent. In SHR, daily oral doses of captopril progressively lowered blood pressure; normal levels were attained by the sixth month. In all species studied, the reduction in blood pressure resulted from a reduction in total peripheral resistance; cardiac output remained unchanged or increased. In humans, captopril reduces blood pressure in patients with essential hypertension with low, normal, and high renin levels, and in patients with renovascular hypertension and hypertension associated with chronic renal failure. In hypertensive patients with high plasma renin activity, captopril apparently exerts most of its pharmacologic effects through inhibition of ACE. The means by which captopril reduces high blood pressure associated with low or normal PRA is not known, but it is clear that captopril does not act on an overactive plasma renin-angiotensin system in these cases. The antihypertensive effect of captopril is enhanced when it is given in combination with a diuretic or after salt depletion. Captopril was rapidly and well absorbed in all species tested, including man. Studies in rodents indicated that ingestion of food caused a reduction in the extent of absorption and bioavailability of captopril. Captopril and/or its metabolites were distributed extensively and rapidly throughout most tissues of normal rats; no radioactivity was detected in the brain. In vitro and in vivo, captopril formed disulfide bonds with albumin and other proteins. This binding was reversible in nature. In vitro studies in blood indicates that the disulfide dimer of captopril and mixed disulfides of captopril with L-cysteine and glutathione were formed. In intact blood cells, captopril remained in the reduced form (sulfhydryl), whereas in whole blood or plasma, captopril was converted to its disulfide dimer and other oxidative products. Biotransformation of captopril may involve both enzymatic and nonenzymatic processes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Captopril: pharmacology, metabolism and disposition. 643 80

Despite intense research efforts, the etiology of primary hypertension remains ill-defined. During our work on molecular influences of lifestyle factors on hypertension, the question arose to what extent cellular and molecular events could be involved in alcohol-induced hypertension. There is increasing evidence that alcohol initiates central as well as peripheral reactions which in a synergistic manner have a hypertensive action. Thus, alcohol diminishes the baro (presso) reflex by interacting with receptors in the brain stem, i.e. nucleus tractus solitarii and rostral ventrolateral medulla. In addition, alcohol induces an increased sympathetic outflow, most probably linked to secretion of corticotropin-releasing hormone. The increased sympathetic outflow is expected not only to induce adrenoceptor-mediated reactions (vasoconstriction, heart rate increase) but to stimulate oxidation reactions. Deleterious peripheral actions result from acetaldehyde which binds to macromolecules if the abundance of cysteine and glutathione is limited. This acetaldehyde induced reduction of low molecular weight thiol compounds can be interpreted as "oxidative stress" which has various unfavourable consequences. The hypertensive action of alcohol should be taken into account when discussing its potential protective influence on coronary risk.
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PMID:[Hypertension and alcohol: central and peripheral mechanisms]. 880 6

This study examined the relationship between homocysteine and its metabolites, and hypertension in a cohort of Sri Lankan patients with essential hypertension. Serum homocysteine, cysteine, cysteinylglycine and glutathione were measured in 86 patients with a diagnosis of essential hypertension and compared with those of an age- and sex-matched control group. Patients with hypertension had significantly higher mean serum concentrations of homocysteine, cysteine and cysteinylglycine. The odds ratio for hypertension for those with a mean serum homocysteine concentration above 18 mumol/l was 2.8. Hyperhomocysteinaemia is a risk factor for hypertension in Sri Lankans and can lead to a threefold increase in risk.
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PMID:Association between hyperhomocysteinaemia and hypertension in Sri Lankans. 1041 60

Full expression of reflex cutaneous vasodilation (VD) is dependent on nitric oxide (NO) and is attenuated with essential hypertension. Decreased NO-dependent VD may be due to 1) increased oxidant stress and/or 2) decreased L-arginine availability through upregulated arginase activity, potentially leading to increased superoxide production through uncoupled NO synthase (NOS). The purpose of this study was to determine the effect of antioxidant supplementation (alone and combined with arginase inhibition) on attenuated NO-dependent reflex cutaneous VD in hypertensive subjects. Nine unmedicated hypertensive [HT; mean arterial pressure (MAP) = 112 +/- 1 mmHg] and nine age-matched normotensive (NT; MAP = 81 +/- 10 mmHg) men and women were instrumented with four intradermal microdialysis (MD) fibers: control (Ringer), NOS inhibited (NOS-I; 10 mM N(G)-nitro-L-arginine), L-ascorbate supplemented (Asc; 10 mM L-ascorbate), and Asc + arginase inhibited [Asc+A-I; 10 mM L-ascorbate + 5 mM (S)-(2-boronoethyl)-L-cysteine-HCl + 5 mM N(omega)-hydroxy-nor-L-arginine]. Oral temperature was increased by 0.8 degrees C via a water-perfused suit. N(G)-nitro-L-arginine was then ultimately perfused through all MD sites to quantify the change in VD due to NO. Red blood cell flux was measured by laser-Doppler flowmetry over each skin MD site, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/MAP) and normalized to maximal CVC (%CVC(max); 28 mM sodium nitroprusside + local heating to 43 degrees C). During the plateau in skin blood flow (Delta T(or) = 0.8 degrees C), cutaneous VD was attenuated in HT skin (NT: 42 +/- 4, HT: 35 +/- 3 %CVC(max); P < 0.05). Asc and Asc+A-I augmented cutaneous VD in HT (Asc: 57 +/- 5, Asc+A-I: 53 +/- 6 %CVC(max); P < 0.05 vs. control) but not in NT. %CVC(max) after NOS-I in the Asc- and Asc+A-I-treated sites was increased in HT (Asc: 41 +/- 4, Asc+A-I: 40 +/- 4, control: 29 +/- 4; P < 0.05). Compared with the control site, the change in %CVC(max) within each site after NOS-I was greater in HT (Asc: -19 +/- 4, Asc+A-I: -17 +/- 4, control: -9 +/- 2; P < 0.05) than in NT. Antioxidant supplementation alone or combined with arginase inhibition augments attenuated reflex cutaneous VD in hypertensive skin through NO- and non-NO-dependent mechanisms.
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PMID:Local ascorbate administration augments NO- and non-NO-dependent reflex cutaneous vasodilation in hypertensive humans. 1748 40

Hypertension is a leading cause of morbidity and mortality worldwide. Individuals with hypertension are at an increased risk for stroke, heart disease and kidney failure. Essential hypertension results from a combination of genetic and lifestyle factors. One such lifestyle factor is diet, and its role in the control of blood pressure has come under much scrutiny. Just as increased salt and sugar are known to elevate blood pressure, other dietary factors may have antihypertensive effects. Studies including the Optimal Macronutrient Intake to Prevent Heart Disease (OmniHeart) study, Multiple Risk Factor Intervention Trial (MRFIT), International Study of Salt and Blood Pressure (INTERSALT) and Dietary Approaches to Stop Hypertension (DASH) study have demonstrated an inverse relationship between dietary protein and blood pressure. One component of dietary protein that may partially account for its antihypertensive effect is the nonessential amino acid cysteine. Studies in hypertensive humans and animal models of hypertension have shown that N-acetylcysteine, a stable cysteine analogue, lowers blood pressure, which substantiates this idea. Cysteine may exert its antihypertensive effects directly or through its storage form, glutathione, by decreasing oxidative stress, improving insulin resistance and glucose metabolism, lowering advanced glycation end products, and modulating levels of nitric oxide and other vasoactive molecules. Therefore, adopting a balanced diet containing cysteine-rich proteins may be a beneficial lifestyle choice for individuals with hypertension. An example of such a diet is the DASH diet, which is low in salt and saturated fat; includes whole grains, poultry, fish and nuts; and is rich in vegetables, fruits and low-fat dairy products.
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PMID:The antihypertensive effect of cysteine. 2247 70

Altered glucose metabolism due to insulin resistance is a common feature of essential hypertension in humans and in animal models. Elevated endogenous aldehydes in genetic (spontaneously hypertensive rats) and acquired (fructose-induced hypertensive rats) models of essential hypertension may be due to increased production of the reactive aldehyde methylglyoxal, resulting from altered glucose metabolism. Excess methylglyoxal binds sulfhydryl groups of membrane proteins, altering calcium channels and increasing cytosolic free Ca(2+) and blood pressure. It has been demonstrated that methylglyoxal, when given in drinking water to Wistar-Kyoto rats, leads to an increase in kidney aldehyde conjugates, cytosolic free Ca(2+) concentration, decreased serum nitric oxide, renal vascular hyperplasia and hypertension. N-acetylcysteine (NAC) in the diet of these animals prevented hypertension and associated biochemical and morphological changes. NAC normalizes blood pressure by directly binding to excess methylglyoxal, thus normalizing Ca(2+) channels, cytosolic Ca(2+) and nitric oxide. NAC also leads to increased levels of tissue glutathione, a storage form of cysteine. Glutathione acts as a cofactor in the enzymatic catabolism of methylglyoxal. Cysteine and other antioxidants, such as vitamins B(6), C and E, and lipoic acid, prevented hypertension and associated biochemical and morphological changes in both genetic and acquired rat models of hypertension. The antihypertensive effect of dietary antioxidants may be due to an increase in tissue cysteine and glutathione, which improves glucose metabolism and decreases tissue methylglyoxal. A diet rich in these antioxidants may be effective in preventing and controlling hypertension in humans.
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PMID:Role of methylglyoxal in essential hypertension. 2247 91

Hypertension is a major health problem worldwide. Individuals with hypertension are at an increased risk for stroke, heart disease, and kidney failure. Although the etiology of essential hypertension has a genetic component, lifestyle factors such as diet play an important role. Insulin resistance is a common feature of hypertension in both humans and animal models affecting glucose and lipid metabolism producing excess aldehydes including methylglyoxal. These aldehydes react with proteins to form conjugates called advanced glycation end products (AGEs). This alters protein structure and function and can affect vascular and immune cells leading to their activation and secretion of inflammatory cytokines. AGEs also act via receptors for advanced glycation end products on these cells altering the function of antioxidant and metabolic enzymes, and ion channels. This results in an increase in cytosolic free calcium, decrease in nitric oxide, endothelial dysfunction, oxidative stress, peripheral vascular resistance, and infiltration of vascular and kidney tissue with inflammatory cells leading to hypertension. Supplementation with dietary antioxidants including vitamins C, E, or B(6), thiols such as cysteine and lipoic acid, have been shown to lower blood pressure and plasma inflammatory cytokines in animal models and humans with essential hypertension. A well-balanced diet rich in antioxidants that includes vegetables, fruits, low fat dairy products, low salt, and includes whole grains, poultry, fish and nuts, lowers blood pressure and vascular inflammation. These antioxidants may achieve their antihypertensive and anti-inflammatory/immunomodulatory effects by reducing AGEs and improving insulin resistance and associated alterations. Dietary supplementation with antioxidants may be a beneficial, inexpensive, front-line alterative treatment modality for hypertension.
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PMID:Role of the immune system in hypertension: modulation by dietary antioxidants. 2320 21

The high prevalence of hypertension contributes to an increased global burden of cardiovascular diseases. Calcium channel blockers (CCBs) and angiotensin type 1 receptor blockers (ARBs) are the most widely used antihypertensive drugs, and the effects of these drugs on serum metabolites remain unknown. Untargeted metabolomics has been proved to be a powerful approach for the detection of biomarkers and new compounds. In this study, we aimed to determine the changes in metabolites after single-drug therapy with a CCB or ARB in patients newly diagnosed with mild to moderate primary hypertension. We enrolled 33 patients and used an untargeted metabolomics approach to measure 625 metabolites associated with the response to a 4-week treatment of antihypertensive drugs. After screening based on P < 0.05, fold change (FC) > 1.2 or FC < 0.83, and variable importance in projection (VIP) > 1, 63 differential metabolites were collected. Four metabolic pathways-cysteine and methionine metabolism, phenylalanine metabolism, taurine and hypotaurine metabolism, and tyrosine metabolism-were identified in participants treated with ARBs. Only taurine and hypotaurine metabolism were identified in participants treated with CCBs. Furthermore, homocitrulline and glucosamine-6-phosphate were relevant to whether the blood pressure reduction achieved the target blood pressure (P < 0.05). Our study provides some evidence that changes in certain metabolites may be a potential marker for the dynamic monitoring of the protective effects and side effects of antihypertensive drugs.
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PMID:Comparative study of metabolite changes after antihypertensive therapy with calcium channel blockers or angiotensin type 1 receptor blockers. 3323 29