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

Endothelial cells produce vasodilator and vasoconstrictor substances. Dietary factors such as sodium, potassium, calcium, magnesium, zinc, selenium, vitamins A, C, and E, and essential fatty acids and their products such as eicosanoids can influence blood pressure, cardio- and cerebrovascular diseases, and concentrations of blood lipids and atherosclerosis. There might be a close interaction between these dietary factors, sympathetic and parasympathetic nervous systems, the metabolism of essential fatty acids, nitric oxide, prostacyclin, and endothelium in human essential hypertension. A deficiency in any one factor, dietary or endogenous, or alterations in their interactions with each other, can lead to endothelial dysfunction and development of hypertension. Therefore, alterations in the metabolism of essential fatty acids might be a predisposing factor to the development of essential hypertension and insulin resistance.
 ...
PMID:Nutritional factors in the pathobiology of human essential hypertension. 1136 75

Endothelial cells are a rich source of a variety of vasoactive substances, which either cause vasodilation or vasoconstriction. Important endothelium-derived vasodilators are prostacyclin, bradykinin, nitric oxide and endothelium-derived hyperpolarizing factor. In particular, nitric oxide inhibits cellular growth and migration. In concert with prostacyclin. nitric oxide exerts potent anti-atherogenic and thromboresistant properties by preventing platelet aggregation and cell adhesion. Endothelium-derived contracting factors include the 21 amino acid peptide endothelin (ET). vasoconstrictor prostanoids such as thromboxane A2 and prostaglandin H2, as well as free radicals and components of the renin angiotensin system. In hypertension, elevated blood pressure transmits into cardiovascular disease by causing endothelial dysfunction. Hence, modem therapeutic strategies in human hypertension focus on preserving or restoring endothelial integrity. Angiotensin converting enzyme (ACE) inhibitors are a primary candidate for that concept as they inhibit the circulating and local renin angiotensin system. Angiotensin converting enzyme is an endothelial enzyme which converts angiotensin-I (A-I) into angiotensin-II (A-II). This effect of the ACE inhibitor prevents direct effects of angiotensin-II such as vasoconstriction and proliferation in the vessel wall but also prevents activation of the ET system and of plasminogen activator inhibitor. Furthermore, inhibition of ACE prolongs the half-life of bradykinin and stabilizes bradykinin receptors linked to the formation of nitric oxide and prostacyclin. In isolated arteries ACE inhibitors prevent the contractions induced by angiotensin II and enhance relaxation induced by bradykinin. Chronic treatment of experimental hypertension with ACE inhibitors normalizes endothelium-dependent relaxation to acetylcholine and other agonists. In addition, the dilator effects of exogenous nitric oxide donors are enhanced, at least in certain models of hypertension. In humans with essential hypertension ACE inhibitors augment endothelium-dependent relaxation to bradykinin, while those to acetylcholine remain unaffected, at least in the time frame of the published studies, i.e. 3-6 months. In patients with coronary artery disease, however, paradoxical vasoconstriction to acetylcholine is markedly reduced after 6 months of ACE inhibition. After myocardial infarction ACE inhibitors reduce the development of overt heart failure, the occurrence of reinfarction and cardiovascular death in hypertensive patients. These effects have also been demonstrated in a subgroup analysis of the SOLVD (Studies of Left Ventricular Dysfunction) trial. Thus, in summary, ACE inhibitors are an important class of drugs providing cardiovascular protection in patients with increased cardiovascular risk.
 ...
PMID:Vascular protective effects of angiotensin converting enzyme inhibitors and their relation to clinical events. 1139 75

Essential hypertension is characterized by significant and persistent elevations in arterial pressure. Hypertension is a multifactorial disorder that may involve abnormalities in the functions of the heart pump, the blood vessels, and the kidneys. Short-term and long-term regulation of arterial pressure is influenced by changes in cardiac function, the peripheral vascular resistance, and the renal control mechanisms of plasma electrolytes and volume. Increases in the heart rate and stroke volume lead to increases in the cardiac output and could contribute to increases in arterial pressure particularly in relatively young individuals. Vascular endothelial cell dysfunction could lead to reduction in endothelium-derived relaxing factors such as nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor, or increased production of contracting factors such as endothelin-1 and thromboxane A2. Also, increased activity of signaling pathways of vascular smooth muscle contraction such as [Ca(2+)]i, protein kinase C, mitogen-activated protein kinase, and Rho kinase could enhance vasoconstriction. The decreased vascular relaxation and excessive vasoconstriction lead to significant increases in the peripheral vascular resistance and arterial pressure over time, particularly with aging. Alterations in body fluid regulation by the kidneys could lead to salt and water retention, increased plasma volume, and cardiac output. Also, activation of the renin-angiotensin system increases the levels of angiotensin II in the plasma, leading to generalized vasoconstriction, or locally in the kidneys, leading to salt and water retention. Individual changes in cardiac, vascular, or renal function seldom occur separately, and, if so, they may lead to mild or moderate increases in arterial pressure. Combined alterations in cardiac, vascular, and renal functions are more common and are often associated with pathologic increases in arterial pressure and established hypertension.
 ...
PMID:Pathophysiology of essential hypertension: role of the pump, the vessel, and the kidney. 1178 64

Prostacyclin inhibits platelet aggregation, smooth muscle cell proliferation, and vasoconstriction. The prostacyclin synthase (PGIS) gene is a candidate gene for cardiovascular disease. The purpose of this study was to locate possible mutations in the PGIS gene related to hypertension and cerebral infarction. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we discovered a T to C transition at the +2 position of the splicing donor site of intron 9 in patients with essential hypertension (EH). In vitro expression analysis of an allelic minigene consisting of exons 8-10 revealed that the nucleotide transition causes skipping of exon 9. This in turn alters the translational reading frame of exon 10 and introduces a premature stop codon (TGA). A three-dimensional model shows that the splice site mutation produces a truncated protein with a deletion in the heme-binding region. This splice site mutation was found in only one subject in 200 EH patients and 200 healthy controls. Analysis of the patient's family members revealed the mutation in two of the three siblings. The urinary excretion of prostacyclin metabolites in subjects with the mutation was significantly decreased. All subjects displaying the splice site mutation in the PGIS gene were hypertensive. In this study, we report a novel splicing mutation in the PGIS gene, which is associated with hypertension in a family. It is thought that this mechanism may involve in the pathophysiology of their hypertension.
 ...
PMID:Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension. 1237 4

The hypertensive disorders of pregnancy, including gestational hypertension, pre-eclampsia and eclampsia, continue to be an important cause of maternal morbidity and mortality. Abnormal placentation is considered to be the main instigating factor, which then leads to widespread maternal endothelial activation and dysfunction. This endothelial perturbation leads to the release of many substances into the circulation, many of which result in platelet activation. For example, there is an imbalance between the levels of prostacyclin (a vasodilator and platelet inhibitor) and thromboxane (a platelet activator and vasoconstrictor), which then results in the maintenance of high blood pressure and complications. It is also likely that platelets play an important part in the pathogenesis of hypertension in pregnancy. The use of antiplatelet drugs has been shown to be effective in reducing the incidence of gestational hypertension in women at high risk and in preventing the complications associated with it. In addition, some antihypertensive agents are effective in reversing platelet activation in essential hypertension and, therefore, their use in pregnancy-induced hypertension may be beneficial in more ways than simply blood pressure reduction.
 ...
PMID:Platelet activation in the hypertensive disorders of pregnancy. 1515 27

Prostacyclin (PGI2) inhibits platelet aggregation and vasoconstriction. Prostacyclin synthase (PGIS), a catalyst of PGI2 synthesis from prostaglandin H2, is widely distributed and predominantly found in vascular endothelial and smooth muscle cells. The PGIS gene is localized to 20q13.11-13, and a candidate gene for cardiovascular disease. We discovered mutations and polymorphisms in this gene and reported that they were associated with essential hypertension, myocardial infarction and cerebral infarction. These results suggest that PGI2 function depends on the different alleles of the PGIS gene and that they may influence the risk of cardiovascular diseases. Thus, individualized management strategies, such as administration of PGI2 analog, could be selected for variants of this gene to help prevent the development of cardiovascular diseases.
 ...
PMID:Prostacyclin synthase gene: genetic polymorphisms and prevention of some cardiovascular diseases. 1585 2

In human essential hypertension (EH), endothelium-dependent relaxation can occur independent of nitric oxide (NO) and prostacyclin (PGI(2)). Recent in vivo data suggest that rapid compensatory upregulation of endothelial cytochrome P450 epoxygenase 2C9 occurs to preserve vasorelaxation under conditions of decreased NO bioavailability. As one of the vascular actions of CYP2C9 is to modulate small and intermediate conductance endothelial calcium-activated potassium channels (SK(Ca) and IK(Ca)), we examined whether endothelium-dependent relaxation is sensitive to inhibitors of these channels (apamin and charybdotoxin) in resistance-sized vessels from human with EH. Subcutaneous gluteal biopsies were performed on 12 humans with EH and 12 matched control subjects. Resistance arteries were dissected and relaxation responses to carbachol were assessed ex vivo using wire myography in the presence of: (i) N(G)-nitro-L-arginine (L-NOARG)/indomethacin; and (ii) apamin/charybdotoxin. Maximal carbachol relaxation was impaired in EH vs control subjects. No differences in responses were observed with the endothelium-independent agonist, S-nitroso-N-acetyl-penicillamine. Relaxation to carbachol was attenuated following incubation with L-NOARG/indomethacin in vessels from control subjects (P<0.01 analysis of variance (ANOVA)), but not in vessels from patients with EH. The reverse pattern was seen following apamin/charybdotoxin with carbachol relaxation attenuated only in EH vessels (P<0.001 ANOVA). Endothelium-dependent relaxation is resistant to endothelial nitric oxide synthase inhibition but sensitive to blockade of calcium-activated potassium channels in human EH. Studies with more specific inhibitors are required to determine whether this response is mediated by endothelial potassium channel subtypes (SK(Ca) and IK(Ca)).
 ...
PMID:Endothelium-dependent relaxation is resistant to inhibition of nitric oxide synthesis, but sensitive to blockade of calcium-activated potassium channels in essential hypertension. 1750 13

Coupling factor 6 (CF6) is composed of 76 amino acids and is present in the peripheral stalk of mitochondrial ATP synthase. The generation of CF6 is positively regulated by tumor necrosis factor alpha and shear stress via nuclear factor kappaB, and by high glucose via protein kinase C and p38 mitogen-activated protein kinase. CF6 is released outside of the cells from vascular endothelial cells, and binds to the beta-subunit of the plasma membrane-bound ATP synthase in vascular endothelial cells and leads to intracellular acidosis. CF6 produces vasoconstriction, and the biological active site resides at the C-terminal portion. CF6 suppresses prostacyclin generation via inhibition of cytosolic phospholipase A(2). CF6 also suppresses nitric oxide synthase activity via an increase in asymmetric dimethylarginine and a decrease in platelet/endothelial cell adhesion molecule-1. CF6 induces the gene and protein expression of proatherogenic molecules such as endothelin 2, urokinase type plasminogen activator receptor, estrogen receptor beta, a soluble short form of vascular endothelial growth factor receptor-1, and lectin-like oxidized low-density lipoprotein receptor-1. The plasma level of CF6 is elevated in patients with essential hypertension, diabetes mellitus, end-stage renal disease, acute myocardial infarction, and coronary heart disease. It is likely that CF6 contributes to the pathogenesis of cardiovascular diseases, but further intensive investigation is needed.
 ...
PMID:Coupling factor 6 as a novel vasoactive and proatherogenic peptide in vascular endothelial cells. 1948 38

Endothelial function is impaired in hypertensive patients. Decreased nitric oxide and prostacyclin production as well as increased oxidative stress are involved in this abnormality. The aim of the present study was to evaluate whether biomarkers of endothelial dysfunction and oxidative stress have diagnostic value in patients with essential hypertension. We measured nitric oxide, prostacyclin, and oxidized-LDL levels and assessed oxidative status in 62 patients with diagnosed essential arterial hypertension and 45 healthy controls. In the hypertensive group, among measured parameters, the median prostacyclin level was significantly lower, when compared to healthy controls (125.57 pg/mL, 25%; 75% quartile range: 84.99; 275.93 and 462.9 pg/mL, 25%; 75% quartile range: 107.69; 849.3, respectively, P = 0.009). The largest area under the ROC curve was found for prostacyclin; 0.647 (95% C.I. 0.549 to 0.737). In the analysis of logistic regression, the prostacyclin and oxidized-LDL cut-off values were associated with a 4.9 higher significant risk of hypertension (O.R. 4.91 and 4.99, respectively; P = 0.0008 and P = 0.00065, respectively). Oxidized-LDL, a biomarker of endothelial damage, was the only one that had a significant negative correlation with protective prostacyclin in hypertensive patients (r = -0.29, P = 0.02). Of all the biomarkers prostacyclin and oxidized-LDL had the best diagnostic value for patients with hypertension.
 ...
PMID:Diagnostic biomarkers of essential arterial hypertension: the value of prostacyclin, nitric oxide, oxidized-LDL, and peroxide measurements. 1950 38

Prostacyclin (PGI2) inhibits platelet aggregation and vasoconstriction. PGI2 synthase (PTGIS), a catalyst of PGI2 synthesis from prostaglandin H2, is widely distributed and predominantly found in vascular endothelial and smooth muscle cells. The PTGIS gene is localized to 20q13.11-13 and a candidate gene for cardiovascular disease. We discovered mutations and polymorphisms in this gene and reported that they were associated with essential hypertension, myocardial infarction, and cerebral infarction. These results suggest that PGI2 function depends on the different alleles of the PTGIS gene and that they may influence the risk of cardiovascular disease. Thus, individualized management strategies, such as the administration of PGI2 analogues, could be selected for variants of this gene, to help prevent the development of cardiovascular disease.
 ...
PMID:Genetic polymorphisms of prostacyclin synthase gene and cardiovascular disease. 2035 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>