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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin as a vascular hormone, apart from its effect on intermediary metabolism, has been considered to play an important role in cardiovascular regulation and pathophysiology of cardiovascular diseases such as essential hypertension, congestive cardiac failure and atherosclerosis. Insulin induces pressor effects by mechanisms of increased sympathetic activity, renal sodium retention and proliferation of vascular smooth muscle cells. On the other hand, accumulating evidence indicates that insulin decreases vascular resistance and increases organ blood flow especially in skeletal muscle tissue, indicating that insulin is a vasodilator. Several mechanisms underlying insulin-induced vasodilation have been proposed. Insulin enhances calcium efflux from vascular smooth muscle cells by activating the plasma membrane Ca(2+)-ATPase and causes hyperpolarization by stimulating Na+, K(+)-ATPase and sodium/potassium pump. Insulin also stimulates nitric oxide (NO) synthase and increases release of NO from vascular endothelium to cause vasodilation. An increase in cyclic AMP levels is induced by insulin, via activation of insulin receptors, beta-adrenoceptors and calcitonin gene-related peptide receptors. However, main cause of mechanisms mediating the vasodilation remain obscure. Hypertension is associated with insulin resistance and hyperinsulinemia. Insulin resistance may contribute to hypertension by sympathetic overactivity, endothelium dysfunction and decreased vasodilator action of insulin. Therefore, insulin must be considered a vasoactive peptide and more investigations are needed to better understand the full significance of the hemodynamic effect of insulin.
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PMID:[Vascular effects of insulin]. 1087 80

Endothelins are potent 21 amino acid vasoconstrictor isopeptides produced in different vascular tissues, including vascular endothelium. Endothelin-1 is the main endothelin generated by the endothelium and probably the most important in the cardiovascular system. Endothelin-1 acts through specific receptors termed ET(A), represented only on smooth muscle cells and having the function of growth promotion and mediating contractions, and ET(B), located both on smooth muscle cells, where they evoke contractions, and on endothelial cells, inducing relaxation by production of the endothelium-derived relaxing factor nitric oxide. In physiological conditions endothelin-1 administration causes vasodilation and vasoconstriction at low and high concentrations, respectively. However, administration of mixed ET(A)/(B) receptor antagonists causes slight or absent vasodilation, indicating that the direct vasoconstrictor effect of the peptide is probably masked by ET(B)-induced NO-dependent vasodilation. In essential hypertensive patients, the activity of exogenous endothelin-1 is either increased, similar or decreased as compared to normotensive subjects, depending on which vascular district or scheme of administration is considered. But although available evidence does not indicate increased endothelin-1 plasma levels in patients with essential hypertension, simultaneous antagonism of ET(A)/(B) receptors causes a greater degree of vasodilation in hypertensives than in normotensive subjects. Moreover administration of a selective ET(B) receptor antagonist causes vasoconstriction in normotensive subjects and vasodilation in essential hypertensive patients. Finally, the vasodilating effect of a mixed ET(A)/(B) receptor antagonist is inversely related to NO availability. Taken together these findings suggest that essential hypertension is characterized by increased endothelin-1 vasoconstrictor tone. This alteration seems to be dependent on decreased endothelial ET(B)-mediated NO production attributable to impaired NO availability. In such conditions endothelial ET(B)-induced vasodilation no longer compensates for the direct classical endothelin vasoconstrictor effect mediated by smooth muscle cell ET(A) and ET(B) receptors. Therefore endothelin-1 could potentially be involved in the pathogenesis of essential hypertension or of its complications, and blockade of this system is a fascinating new target for therapeutic intervention in this disease.
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PMID:Role of endothelin in the control of peripheral vascular tone in human hypertension. 1144 2

An interaction between homocyst(e)ine and the endothelium in hypertensive patients may promote thrombogenesis and atherogenesis, leading to adverse cardiovascular events. We hypothesized that homocyst(e)ine levels are abnormal in patients with essential hypertension, and that this may be related to an adverse effect on the vascular endothelium. Accordingly, we compared plasma levels of homocyst(e)ine and von Willebrand factor (marking endothelial damage) in 83 patients (43 men; mean age 54 +/- standard deviation 15.9 years) with essential hypertension (> 160/90 mm Hg), with levels in 25 healthy normotensive controls (13 men; mean age 56+/-11.8 years). Baseline levels of the markers and other clinical indices were then related to adverse cardiovascular events at follow-up. Plasma homocyst(e)ine (P = .0001) and von Willebrand factor (P = .031) levels were significantly higher in hypertensives compared to controls. After a mean follow-up of 76 patients for 45 months (range, 1 to 66 months), 17 subjects experienced an end point of either cardiovascular death (n = 10) or adverse cardiovascular event (n = 7). Comparing these 17 with the 59 free of an end point, the former were older (P = .0002) and had a longer duration of known hypertension (P = .018). There was a nonsignificant trend toward higher median plasma homocyst(e)ine levels in the patients sustaining a vascular end point (P = .07). In this pilot study, we suggest that essential hypertension may be associated with increased plasma homocyst(e)ine levels, but that this amino acid is unrelated to endothelial damage (von Willebrand factor), clinical indices, or prognosis.
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PMID:A pilot study of homocyst(e)ine levels in essential hypertension: relationship to von Willebrand factor, an index of endothelial damage. 1146 45

Nitric oxide(NO), a potent vasodilator produced by endothelial cells, plays an important role in the regulation of blood pressure and regional blood flow, and also inhibits platelet aggregation and leukocyte adhesion to vascular endothelium and inhibits vascular smooth muscle cell proliferation. Various genetic polymorphisms of the endothelial nitric oxide synthase(eNOS) gene have been reported as susceptibility genes in a number of cardiovascular diseases. The functional significance of these polymorphisms has not yet been demonstrated, but recent study revealed that eNOS Glu298Asp variant is likely to have a functional effect on the eNOS protein. The missense Glu298Asp variant was correlated with increased coronary spasm, myocardial infarction, essential hypertension, left ventricular hypertrophy, carotid atherosclerosis, and cerebral infarction.
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PMID:[NOS gene polymorphism]. 1473 42

We have shown that the capacity for local release of tissue-type plasminogen activator (tPA) from the vascular endothelium is impaired in patients with primary hypertension. Because this response is an important protective mechanism against intravascular clotting, we investigated whether this system is also defective in patients with advanced chronic kidney disease and hypertension. Nine nondiabetic nonsmoking men with chronic kidney disease (glomerular filtration rate 11 to 28 mL/min x 1.73 m2; aged 33 to 75 years) were compared with age-matched healthy controls. Intraarterial infusions of desmopressin, methacholine, and sodium nitroprusside were given locally in the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography and blood collected repeatedly during the desmopressin infusion for determination of stimulated net and total cumulated release of tPA. The maximal release rate of active tPA (P<0.05) and the capacity for acute tPA release were markedly impaired in the renal patients as compared with healthy subjects (ANOVA, P=0.013). Accordingly, the accumulated release of tPA was 1905 (SEM 366) and 3387 (718) ng/L tissue, respectively (P<0.05). However, there were no significant differences in vasodilator responses between the groups. Thus, patients with advanced chronic kidney disease and hypertension have a markedly impaired capacity for acute release of tissue plasminogen activator, despite preserved endothelium-dependent vasodilation. This defect may contribute to a defective local defense against arterial thrombosis.
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PMID:Impaired endothelial release of tissue-type plasminogen activator in patients with chronic kidney disease and hypertension. 1524 48

The etiology of preeclampsia (PE) is unknown, but endothelial cell injury plays a pivotal role. Moreover, there is a significantly positive association between PE and later hypertension. Apolipoprotein J (apo J) plays an important role in stabilizing cell membranes at diverse fluid-tissue interfaces and might protect vascular endothelium against an attack by some factors in plasma such as active complement complexes. This study investigated the prevalence and possible association of apo J gene in PE and essential hypertension (EH). To screen for polymorphisms of apo J gene in a population in Guizhou, China, by employing polymerase chain reaction combined with denaturing gradient gel electrophoresis, we identified 866C-->T polymorphism in exon 5 and a rare variant 1061C-->T in exon 7. The CT genotype and T-allele frequencies in PE (CT genotype 26%; T allele 13%) and EH (CT genotype 28.57%; T allele 17.14%) were significantly lower than that in the control group (CT geno type 50%; T allele 27%). The results suggested that the 866C-->T polymorphism might be associated with PE and EH. It is plausible that apo J may play a certain role in the predisposition to PE and EH.
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PMID:Association of apolipoprotein J gene 866C-->T polymorphism with preeclampsia and essential hypertension. 1592 90

Hypertension is a major risk factor for atherosclerotic cardiovascular disease. Selectins, cell-surface adhesion molecules involved in leukocyte rolling and attachment to the vascular endothelium, play a role in the initiation of atherosclerosis. We investigated whether or not serum levels of soluble adhesion molecules are elevated in patients with essential hypertension (EH) and examined whether antihypertensive therapy lowers such levels. Twenty-one patients who had untreated mild to moderate EH without diabetes mellitus, hyperlipidemia, or obesity were recruited at a clinic for hypertensive patients. Blood pressure was measured, and the serum levels of soluble E-selectin, P-selectin, L-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular-cell adhesion molecule 1 (VCAM-1) were determined by enzyme-linked immunosorbent assays before and after 12, 24, and 53 weeks of antihypertensive treatment with benidipine, a long-acting calcium channel blocker, given at a dose of 6 mg/day for 53 weeks. As a control, 21 age- and sex-matched patients without hypertension were studied. Serum E- and P-selectin levels were significantly higher in the subjects with EH than in the controls (p < 0.01). There were no differences in serum levels of soluble L-selectin, VCAM-1, or ICAM-1 levels between the patients with EH and the controls. Treatment with benidipine decreased the elevated blood pressure over a 53-week study period (mean blood pressure: 119.8 +/- 6.5 mmHg at baseline, 101.0 +/- 5.9 mmHg at 12 weeks, 98.6 +/- 7.3 mmHg at 24 weeks, and 93.9 +/- 5.5 mmHg at 53 weeks). Serum levels of soluble E- and P-selectin decreased after the initiation of benidipine treatment and correlated with diastolic blood pressure. Serum levels of soluble L-selectin, VCAM-1, and ICAM-1 did not change significantly during the period of benidipine treatment. Benidipine treatment reduced the content of P-selectin in the platelets from patients with EH, as determined by Western blot analysis. In conclusion, decreased blood pressure may reduce the rate of progression of atherosclerosis by affecting the expression of E- and P-selectin in the endothelium, the platelets, or both. Benidipine may be protective against vascular damage in people with hypertension, not only by lowering blood pressure, but also by inhibiting the expression of selectins.
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PMID:Elevation of serum soluble E- and P-selectin in patients with hypertension is reversed by benidipine, a long-acting calcium channel blocker. 1655 75

Endothelial function is impaired in essential hypertension. T-type but not L-type voltage-gated Ca2+ channels were detected in the vascular endothelium. The purpose of the present study was to clarify the role of T-type Ca2+ channels in endothelial function. We studied flow-mediated vasodilation (FMD) and sublingual nitroglycerin (NTG)-induced vasodilation in the brachial artery. Forty patients with essential hypertension were randomly assigned to treatment with efonidipine, a T- and L-type Ca2+ channel blocker, or with nifedipine, an L-type Ca2+ channel blocker. Twenty healthy normotensive individuals were included as a control group. In patients with essential hypertension, FMD was attenuated and NTG was similar that of compared to healthy controls. After 12 weeks, the decrease in mean blood pressure in the efonidipine and nifedipine groups were similar. The endothelial function index, a ratio of FMD/NTG, was significantly increased by efonidipine (73 +/- 24 to 94 +/- 20%) but unchanged by nifedipine. Urinary excretion 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum malondialdehyde-modified low-density lipoprotein (LDL) were decreased by efonidipine but unchanged by nifedipine. These results suggest that a T-type Ca2+ channel blocker, but not an L-type Ca2+ channel blocker, may improve vascular endothelial dysfunction in patients with essential hypertension via a reduction in oxidative stress.
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PMID:Beneficial effect of T-type calcium channel blockers on endothelial function in patients with essential hypertension. 1655 77

Renal insufficiency in essential hypertension represents the expression of a medium- and small-size arteriolopathy characterized by intimal hyperplasia, hyalinosis, and smooth muscle cell hypertrophy (nephroangiosclerosis). Because in animal models endothelial dysfunction plays a role in this alteration, nephroangiosclerosis and the attendant renal insufficiency may be the expression of a systemic dysfunction of vascular endothelium. Endothelial function in the kidney vasculature of hypertensive individuals has been investigated little because studies on the hemodynamic response of the kidney to nitric oxide activation and blockade are laborious to perform. There is no direct proof that endothelial dysfunction in the forearm or in the coronary circulation is paralleled by a similar hemodynamic dysfunction in the kidney. A recent study in a large population of patients with essential hypertension showed that, independent of other risk factors, the GFR in these patients is strongly related to the forearm blood flow response to acetyl choline (an established test of endothelial function). Furthermore, in this study, C-reactive protein was inversely related to the GFR and with the vasodilatory response to acetyl choline, pointing to inflammation as a likely mechanism to explain the association between endothelial dysfunction and impaired renal function in essential hypertension. A dysfunctional endothelium may represent a critical link accounting for the risk for both renal impairment and cardiovascular complications in essential hypertension.
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PMID:Endothelial dysfunction and the kidney: emerging risk factors for renal insufficiency and cardiovascular outcomes in essential hypertension. 1656 49

Synthetic big endothelin-1 (ET-1), a 39-residue precursor of ET-1, has been reported to elicit potent contractile action on helical strip specimens obtained from the porcine coronary artery, but its molar potency was found to be 140-fold lower than that of ET-1 [Saito, Y., Nakao, K., Mukoyama, M., Imura, H., 1990. Increased plasma endothelin level in patients with essential hypertension. N. Engl. J. Med. 322, 205]. It has been hypothesized that the increased rate of production and/or release of ET-1 from the vascular endothelium may contribute to the pathogenesis of hypertension. However, the effects of big ET-1 in comparison with ET-1 on the macrocirculation and microcirculation of the rat mesentery have not been well documented. Thus, our main purpose for this study was to examine the effects of both big ET-1 and ET-1 to clarify the role of phosphoramidon in inhibiting the conversion of big ET-1 to ET-1, by investigating the systemic blood pressure, microvascular blood flow velocity, and diameters of arterioles and venules of the rat mesentery. For this purpose, two groups of experiments were performed. In these experiments, the mesentery was arranged for in situ intravital microscopic observation under transillumination. In the first group of experiments, intravenous cumulative injections of big ET-1 or ET-1 were infused through a catheter inserted into the right jugular vein. Infusion of big ET-1 (1-8 nmol/kg) elicited a long-lasting significant pressor effect. Infusion of big ET-1 (1-2 nmol/kg) elicited a significant dose-dependent increase in the microvascular blood flow velocity both in arterioles (20-30 microm) and venules (30-40 microm). Microvascular diameters exhibited a slight but significant vasodilator effect. However, the infusion of big ET-1 (4-8 nmol/kg) elicited a dose-dependent significant decrease in the blood flow velocities, and diameters returned to control measurements. The administration of ET-1 (0.25-2 nmol/kg) induced a dose-dependent significant decrease in the blood flow velocity of arterioles and venules, and their diameters exhibited a vasoconstrictive effect more prominent in arterioles than in venules. In the second group of experiments, cumulative injections of phosphoramidon (30 mg/kg/10 min) were administered 10 min prior to the infusion of big ET-1. Phosphoramidon significantly suppressed the long-lasting significant pressor effect and significantly inhibited the dose-dependent increase and dose-dependent decrease in the microvascular blood flow velocity produced by big ET-1 in the rat mesenteric microcirculation. This study observed differences in the effects big ET-1 and ET-1 have on the rat mesenteric microcirculation and proposes a possible mechanism explaining these differences. Moreover, phosphoramidon markedly inhibited the conversion of big ET-1 to ET-1 in the rat mesenteric microcirculation, which may suggest an inhibition of the enzyme which converts big ET-1 to ET-1.
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PMID:Effects of big endothelin-1 in comparison with endothelin-1 on the microvascular blood flow velocity and diameter of rat mesentery in vivo. 1702 40


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