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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review discusses the role of three mediators, synthesized by vascular endothelial cells, that help to keep the surface of the normal endothelium nonthrombogenic. The first is prostacyclin, a product of arachidonic acid metabolism discovered in 1976. This labile prostanoid, with a half-life of approximately 3 minutes, relaxes vascular smooth muscle and inhibits the aggregation of blood platelets. Prostacyclin and its analogues are currently being tested clinically for use in cardiovascular diseases such as primary pulmonary hypertension. The second mediator discussed is endothelium-derived relaxing factor (EDRF), discovered in 1980, which also relaxes smooth muscle and inhibits the aggregation and adhesion of platelets. Substances that stimulate the release of EDRF include acetylcholine, bradykinin, and adenosine 5'-diphosphate. EDRF is even more labile than prostacyclin, with a half-life of about 6 seconds, and it has recently been identified as nitric oxide. Prostacyclin and EDRF are released together following stimulation of endothelial receptors and synergize to inhibit platelet aggregation. 13-Hydroxy-9,11-octadecadienoic acid, a third suggested mediator, is not released but acts from inside the cell to make the endothelial surface nonadhesive for circulating blood cells. It is proposed that these three mediators form the endothelial defense mechanism against blood-borne cells and chemicals and that breakdown of this barrier results in diseases such as hypertension and atherosclerosis.
Hypertension 1988 Dec
PMID:Mediators produced by the endothelial cell. 306 Apr 28

2-Hydroxy-(1-hydroxy-[(1-methyl-3-phenylpropyl)amino]-2-ethyl)-5-benzamide (labetalol), a new alpha- and beta-adrenergic blocking agent, was employed in 21 patients with severe hypertension by slow (6 patients) and rapid (15 patients) i.v. infusion. A marked and significant fall of blood pressure was observed in both groups, though more gradual in patients treated by slow infusion. A rapid blood pressure fall with cardiac output decrease was observed by passing from supine to standing position in the first hours after infusion. Therefore, it is advisable to keep a supine position for a few hours. Plasma renin activity decreased after labetalol infusion, but basal plasma renin levels were not related to hypotensive effect of labetalol. In slow infusion patients, plasma noradrenaline levels increased and no changes of plasma adrenaline levels were observed during infusion. The most likely explanation of these variations is an increase of sympathetic activity secondary to hypotension, caused by labetalol, whereas a technical interference seems to be excluded. The simultaneous blockade of alpha- and beta-receptors can inhibit, in this case, the pressor effects of the sympathetic reflex.
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PMID:Intravenous labetalol in severe hypertension. Effects on blood pressure, plasma renin activity and catecholamines. 701 70

In addition to the hemodynamic components, the roles of various humoral factors have been emphasized in the progression of vascular and renal injury in hypertension. Radical scavenging properties have attracted much attention in this field. This article discusses the implication of antioxidant properties of the antihypertensive diuretic indapamide on renal injury in Dahl salt-sensitive (Dahl S) rats. Hydroxyl radicals, oxygen radicals toxic to cellular membranes, are eradicated by indapamide in different assay systems, e.g., reduction of alpha-alpha-diphenyl-beta-picrylhydrazyl, rat brain homogenate, or xanthine-xanthine oxidase systems. Such antioxidant effects of indapamide are primarily due to inhibition of lipid peroxidation induced by hydroxyl radicals, and this mechanism may stimulate prostacyclin generation through activation of prostacyclin synthase. In fact, the antioxidant properties of indapamide are well expressed in vivo as well; indapamide treatment reduced oxygen radicals in the kidney of Dahl S rats with hypertension. This was accompanied by a functional improvement of the kidney; decreases in urinary protein and n-acetylglucosaminidase excretion and an increase in glomerular filtration rate were observed. In addition, indapamide morphologically ameliorated the renal injury, and decreased glomerular sclerosis score, arterial injury, and renal tubular injury. Trichloromethiazide reduces blood pressure similar to that produced by indapamide. However, trichloromethiazide did not lead to reduction of oxygen radicals in the kidney, and did not improve the functional disturbance or morphological injury seen in Dahl S rats. These results indicate that indapamide has antioxidant properties, and in addition to blood pressure reduction, such radical scavenging effects may contribute to its beneficial effects on renal function in vivo.
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PMID:Oxygen radical scavengers and renal protection by indapamide diuretic in salt-induced hypertension of Dahl strain rats. 750 60

In 76 consecutive patients who had received diuretics for 1-17 years for arterial hypertension or congestive heart failure, muscle concentrations of magnesium, potassium, and sodium-potassium pumps were significantly reduced compared to 31 age- and sex-matched controls. Thirty-six patients with muscle magnesium and/or potassium below the control level received oral magnesium hydroxide supplement for 2-12 weeks (N = 20) or 26 weeks (N = 16). After short term (2-12 weeks) magnesium supplementation muscle parameters were increased, but far from normalized. After magnesium supplementation for 26 weeks, the muscle concentrations of magnesium, potassium and sodium-potassium pumps were normalized in most cases. Oral magnesium supplementation may restore diuretic-induced disturbances in the concentrations of magnesium, potassium and sodium-potassium pumps in skeletal muscle. A supplemental period of at least six months seems required before complete normalization can be expected.
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PMID:[Oral magnesium supplementation to patients receiving diuretics--normalization of magnesium, potassium and sodium, and potassium pumps in the skeletal muscles]. 806 94

In 76 consecutive patients who had received diuretics for 1-17 years for arterial hypertension or congestive heart failure, muscle concentrations of magnesium, potassium, and sodium-potassium pumps were significantly reduced compared to 31 age- and sex-matched controls. Thirty-six patients with muscle magnesium and/or potassium below the control level received oral magnesium hydroxide supplement for 2-12 weeks (n = 20) or 26 weeks (n = 16). After short-term (2-12 weeks) magnesium supplementation muscle parameters were increased, but far from normalized. After magnesium supplementation for 26 weeks, the muscle concentrations of magnesium, potassium and sodium-potassium pumps were normalized in most cases. Oral magnesium supplementation may restore diuretic-induced disturbances in the concentrations of magnesium, potassium and sodium potassium pumps in skeletal muscle. A supplemental period of at least 6 months seems to be required before complete normalization can be expected.
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PMID:Oral magnesium supplementation restores the concentrations of magnesium, potassium and sodium-potassium pumps in skeletal muscle of patients receiving diuretic treatment. 838 50

Cardiac allograft vasculopathy (CAV) remains a troublesome long-term complication of heart transplantation. It is manifested by a unique and unusually accelerated form of coronary disease affecting both intramural and epicardial coronary arteries and veins.CAV is characterized by vascular injury induced by a variety of noxious stimuli, including the immune system response to the allograft, ischemia-reperfusion injury, viral infection, immunosuppressive drugs, and classic risk factors such as hyperlipidemia, insulin resistance, and hypertension. The obstructive vascular lesions are thought to progress through repetitive endothelial injury followed by repair response. The role of major histocompatibility complex donor-recipient differences in the pathogenesis of CAV has not yet been completely elucidated. Intracoronary ultrasound studies reveal a dual morphology with donor-transmitted or de novo focal, noncircumferential plaques in proximal segments and/or a diffuse, concentric pattern observed in distal segments. A lack of correlation between microvascular and epicardial vessel disease suggests discordant manifestations and progression of CAV. Apoptosis and loss of functional vascular remodeling have to be considered as important mediators of clinically relevant CAV. Strategies for blocking T-cell costimulation and expression of adhesion molecules may help prevent chronic rejection in clinical transplantation. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and antiproliferative drugs may slow progression of CAV by various effects. Methods to augment endogenous nitric oxide bioavailability as well as newer immunosuppressive regimens may be protective. Balloon angioplasty has a limited role in the treatment of focal lesions. Experiences with coronary stenting, coronary artery bypass grafting, and transmyocardial laser revascularization are limited. Retransplantation has a worse outcome than initial transplantation.
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PMID:Cardiac allograft vasculopathy: a review. 932

Recently, we reported that primary cultures of inner medullary collecting duct cells from Dahl salt-sensitive (S) rats absorb more Na+ than do cells cultured from Dahl salt-resistant (R) rats. To begin to evaluate the molecular basis for this difference, we selected four candidate gene products that on the basis of their physiology and genetics could participate in regulation of Na+ transport by these cells. During 24-hour exposure, inhibitors of the cytochrome P450 enzymes had no effect on Na+ transport by either S or R monolayers. Twenty-four-hour exposure to NG-monomethyl-L-arginine (0.5 mmol/L), a nonspecific inhibitor of NO synthase, also had no effect on Na+ transport by either S or R monolayers. Neither atrial natriuretic peptide 1-28 (100 nmol/L) nor 8-Br-cyclic GMP (100 micromol/L) had any short-term effect on Na+ transport by either S or R monolayers. 18-Hydroxy-11-deoxycorticosterone (100 nmol/L), an adrenocorticoid hormone that is produced in greater amounts in S rats, stimulated Na+ transport by both S and R monolayers via the mineralocorticoid receptor; however, its effect was less potent than aldosterone. Congenic rats in which the R isoform of the 11beta-hydroxylase gene was bred onto the S background had monolayers that transported Na+ at a rate similar to the S rats. These results demonstrate that neither cytochrome P450 genes, NO synthase genes, the atrial natriuretic peptide receptor gene, nor the 11beta-hydroxylase gene is a likely candidate to explain the difference in Na+ transport between S and R inner medullary collecting duct monolayers in primary culture.
Hypertension 1998 Feb
PMID:Candidate genes in the regulation of Na+ transport by inner medullary collecting duct cells from Dahl rats. 946 Dec 29

This article, based on our own studies and those of others, presents evidence to show that the anemia of chronic renal failure in the predialysis period is, to a significant extent, caused by iron deficiency and can be improved in most cases by the administration of intravenous (i.v.) but not oral iron. We estimate that in approximately 30% of all predialysis patients with anemia, a target hematocrit (Hct) of 35% can be reached and maintained by giving i.v. iron alone without exceeding currently acceptable limits of serum ferritin (500 microg/liter) or the percentage of iron saturation (40%). If, in addition, subcutaneous erythropoietin (EPO-usually in only low doses-is added, the combination has an additive effect on the Hct response, and almost all anemic predialysis patients can reach and maintain the target Hct of 35% over a one-year period. Therefore, the advantage of maintaining adequate iron stores with i.v. iron is that if EPO is needed, lower doses will be required to achieve the target Hct than if EPO were used alone. This not only avoids the high cost of EPO therapy but also its associated side-effects, especially hypertension. Using Venofer, a ferric hydroxide sucrose complex, as our i.v. iron supplement, we have seen no anaphylactic reactions in over 20,000 infusions over a four-year period in 360 hemodialysis, 123 predialysis, and 58 peritoneal dialysis patients.
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PMID:Intravenous iron for the treatment of predialysis anemia. 1008 91

Three separate studies were undertaken in HIV-1 uninfected persons to determine if the adjuvant QS-21 improves the magnitude or kinetics of immune responses induced by recombinant soluble gp120 HIV-1(MN) protein (rsgp120) immunization. The QS-21 was administered at two doses (50 and 100 microg), either alone or in combination with aluminum hydroxide (600 microg). At the highest doses of rsgp120 (100, 300, and 600 microg), QS-21 exerted no significant effect on either binding or neutralizing antibody titers. Antibody binding and neutralizing responses fell dramatically when rsgp120, formulated with alum alone, was given at low doses (3 and 30 microg). In contrast, antibody responses similar in titer to those in the high dose antigen groups were induced with the low dose rsgp120 formulated with QS-21. In addition, the lymphocyte proliferation and delayed type hypersensitivity skin testing were superior in the QS-21 recipients compared with the alum recipients at the low antigen doses. Moderate to severe pain was observed in majority of the volunteers receiving QS-21 formulations, and vasovagal episodes and hypertension were not infrequent. Thus, the use of QS-21 may provide a means to reduce the dose of a soluble protein immunogen.
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PMID:QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1 envelope subunit immunization in humans. 1122 80

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) significantly reduce cardiovascular mortality associated with hypercholesterolemia. There is evidence that statins exert beneficial effects in part through direct effects on vascular cells independent of lowering plasma cholesterol. We characterized the effect of a 30-day treatment with atorvastatin in normocholesterolemic, spontaneously hypertensive rats (SHR). Systolic blood pressure was significantly decreased in atorvastatin-treated rats (184+/-5 versus 204+/-6 mm Hg for control). Statin therapy improved endothelial dysfunction, as assessed by carbachol-induced vasorelaxation in aortic segments, and profoundly reduced angiotensin II-induced vasoconstriction. Angiotensin type 1 (AT(1)) receptor, endothelial cell NO synthase (ecNOS), and p22phox mRNA expression were determined with quantitative reverse transcription-polymerase chain reaction. Atorvastatin treatment downregulated aortic AT(1) receptor mRNA expression to 44+/-12% of control and reduced mRNA expression of the essential NAD(P)H oxidase subunit p22phox to 63+/-7% of control. Aortic AT(1) receptor protein expression was consistently decreased. Vascular production of reactive oxygen species was reduced to 62+/-12% of control in statin-treated SHR, as measured with lucigenin chemiluminescence assays. Accordingly, treatment of SHR with the AT(1) receptor antagonist fonsartan improved endothelial dysfunction and reduced vascular free-radical release. Moreover, atorvastatin caused an upregulation of ecNOS mRNA expression (138+/-7% of control) and an enhanced ecNOS activity in the vessel wall (209+/-46% of control). Treatment of SHR with atorvastatin causes a significant reduction of systolic blood pressure and a profound improvement of endothelial dysfunction mediated by a reduction of free radical release in the vasculature. The underlying mechanism could in part be based on the statin-induced downregulation of AT(1) receptor expression and decreased expression of the NAD(P)H oxidase subunit p22phox, because AT(1) receptor activation plays a pivotal role for the induction of this redox system in the vessel wall.
Hypertension 2001 Jun
PMID:HMG-CoA reductase inhibitors improve endothelial dysfunction in normocholesterolemic hypertension via reduced production of reactive oxygen species. 1140 94


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