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

In normal pregnancy, increased production of platelet thromboxane A2(TXA2) parallels increased biosynthesis of vascular prostacyclin (PGI2). An imbalance in the formation of these prostaglandins is believed to be associated with the pathogenesis of pregnancy-induced hypertension (PIH). Recent evidence suggested that aspirin in low doses was effective in reducing the incidence of PIH, by selective inhibition of platelet-derived TXA2 biosynthesis. In this communication, we determined the urinary 11-dehydro TXB2 and 6-keto-PGF1 alpha, which are major metabolites of TXA2 and PGI2, respectively, from early to late pregnancy of normal pregnant women and of women complicated with PIH. The ratio of 11-dehydro TXB2 to 6-keto-PGF1 alpha decreased significantly from as early as 10wks of gestation when compared with that in non-pregnant controls (1.43 +/- 0.15 vs 1.99 +/- 0.13: Mean +/- SEM, p less than 0.05), and increased in later pregnancy to the control values at term. No significant difference was found in the excretion of 11-dehydro TXB2 between normal pregnant women and women with PIH. In contrast, urinary excretion of 6-keto-PGF1 alpha decreased in women with PIH. The ratio of 11-dehydro TXB2 to 6-keto-PGF1 alpha increased significantly as compared with that of pregnant controls. These results demonstrated that disturbed production of vascular PGI2 may be the primary cause of PIH, and affect the vascular responsiveness to pressor inducers such as angiotensin II.
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PMID:[Urinary 11-dehydrothromboxane B2 and 6-keto-prostaglandin F1 alpha in normal pregnant women and in women complicated with pregnancy-induced hypertension]. 150 26

The endothelium not only mediates relaxation but is a source of contracting factors. Endothelium-dependent contractions are elicited by physical and chemical stimuli (i.e., hypoxia, pressure, and stretch) and autacoids, local and circulating hormones. The mechanism of endothelium-dependent contractions to hypoxia involves withdrawal of nitric oxide. The endothelial cyclooxygenase pathway can produce thromboxane A2, prostaglandin H2, and superoxide anions. The peptide endothelin is a potent contracting factor; its production is stimulated by vasopressor hormones, platelet-derived factors, coagulation products, and cytokines, whereas endothelium-derived nitric oxide, prostacyclin, and a smooth muscle cell-derived inhibitory factor reduce endothelin production. In hypertension, the release of cyclooxygenase-dependent endothelium-derived contracting factors to stretch, acetylcholine, and platelet-derived products is augmented. Vascular endothelin production in hypertension remains controversial but appears mostly normal; it is augmented in the presence of vascular disease or renal insufficiency. The endothelium-dependent inhibition of endothelin-induced contractions is reduced in hypertension while the reactivity of vascular smooth muscle may be normal, increased, or reduced. The potentiating effects of low concentrations of endothelin on contractions to norepinephrine are augmented with aging and hypertension. In atherosclerosis, the production of the cyclooxygenase-dependent endothelium-derived contracting factors and endothelin is enhanced. Thus, endothelium-derived contracting factors can profoundly affect vascular tone and counteract relaxing factors produced within the endothelium. In hypertension and atherosclerosis, the role of contracting factors appears to become more dominant, leading to an imbalance of endothelium-dependent vascular regulation.
Hypertension 1992 Feb
PMID:Endothelium-derived contracting factors. 173 45

While the roles of the platelet-derived growth factors (PDGFs) in vascular smooth muscle cells (SMCs) continue to be elucidated, these cells, especially in their activated 'synthetic' state, have also been found to express, and proliferate in response to, many of the other families of polypeptide growth factors, such as the fibroblast growth factors. Other stimulators of DNA synthesis, and particularly of SMC hypertrophy, include the vasoconstrictor hormones such as angiotensin II, as well as physical forces, especially stretch or tension. For many of these ligands, multiple receptors have been identified and their means of signal transduction are being characterized rapidly. Regulatory regions of these genes are being identified as are transcription factors. Complex post-transcriptional regulation has also been shown by the findings that some growth factors are phosphorylated, or translocated to the nucleus or the extracellular matrix. Inhibitors have also been identified. These include some prostaglandins, calcium antagonists, agonists that activate guanylate and adenylate cyclases, inhibitors of angiotensin-converting enzyme, interferon gamma, and heparin. Future studies are likely to show that tyrosine phosphatases and recessive oncogenes also regulate growth. The existence of so many autocrine/paracrine mitogens--together with some experimental data--suggests some redundancy in the system as well as some additive effects. Redundancy may limit the efficacy of antibodies to a single growth factor to block cell proliferation. Their evolutionary conservation implies some unique roles for each growth factor but these have not been apparent from in vitro studies to date. Further insights are apt to come from the increasing recognition that growth factors have other effects--on cell attachment, migration, survival, production of extracellular matrix, thrombosis, vaso-constriction, regulation of cytokine synthesis, and inhibition of growth. Many of these effects may prove to be context-dependent, as with the case of growth inhibition by transforming growth factor-beta. Studies in monolayer cultures may not obtain the same results as studies using cocultures of endothelial and smooth muscle cells, or 3-dimensional matrix cultures, organ cultures, or in the intact animal. In vivo descriptive studies of growth factors expressed in vascular embryogenesis, hypertension, atherosclerosis, acute balloon injury and thrombosis are being supplemented by interventions such as infusions with growth factors, antibodies, and toxin conjugates. These studies, and studies using transgenic mice and homologous recombination, should yield information as to mechanisms and may also suggest new therapies.
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PMID:Smooth muscle cell growth factors. 181 90

We recently described the early appearance of pulmonary hypertension in the fawn-hooded rat (FHR), an animal with platelet storage pool disease also known to develop systemic hypertension at later ages. Since mediators released from aggregating platelets influence vascular tone, we hypothesized that platelet-mediated pulmonary vascular responses in FHR may be abnormal and potentially linked to the mechanism of pulmonary hypertension. To test this we examined reactivity of isolated pulmonary arteries (PA) and thoracic aortas (Ao) from young FHR with moderately severe pulmonary hypertension but normal systemic pressures. These vessels were compared with PA and Ao from control Sprague-Dawley rat (SDR). Aggregating platelets (1,000-40,000 platelets/mm3) from FHR caused dilation of SDR PA and Ao but constriction of FHR PA and Ao. Qualitatively similar responses were also observed with platelets isolated from SDR implying that abnormal responses were not simply due to the storage pool deficiency in FHR. Response to the platelet-derived endothelium-dependent vasodilator ADP was markedly impaired in FHR PA and mildly impaired in FHR Ao. Endothelium-dependent dilation to acetylcholine, but not to A23187, was mildly impaired in FHR PA while responses to both dilators were normal in FHR Ao. Endothelium-independent dilation to sodium nitroprusside was normal in both FHR PA and Ao. Constrictor sensitivity to serotonin, but not to the thromboxane A2 mimetic U-46619, was increased in FHR PA while responses to both constrictors were normal in FHR Ao. In summary, PAs from FHR with spontaneous pulmonary hypertension exhibit paradoxical constriction to both normal and storage pool deficient platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Paradoxical constriction to platelets by arteries from rats with pulmonary hypertension. 182 34

Diabetes mellitus is a major risk factor for coronary heart disease, peripheral vascular disease, and cardiovascular disease. The prevalence of these complications is increased about two- to four-fold in people with diabetes in the United States, and they contribute substantially to morbidity, mortality, and healthcare costs. The pathogenesis of macrovascular disease in diabetes is multifactorial. Endothelial injury is an early event, followed by macrophage adherence and uptake of lipids to produce a fatty streak. Platelet adherence, aggregation, and release of thromboxane and platelet-derived growth factors may then occur. Quantitative and qualitative alterations of lipoproteins are seen, particularly in uncontrolled insulin-dependent and non-insulin-dependent diabetes. Hyperinsulinemia may be contributory, as may elevated plasma proinsulin levels. Glycation of plasma proteins and of components of the vascular wall occurs, and altered coagulation and/or fibrinolysis may lead to thrombosis. The process is accelerated by hypertension, smoking, and hypercholesterolemia. Gliclazide is an oral sulfonylurea agent that has been reported to have actions on platelet function and fibrinolysis in addition to its effects on glycemia. The evidence for this is reviewed, and recommendations for future studies are made.
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PMID:Pathophysiology of vascular disease in diabetes: effects of gliclazide. 187 5

Endothelial cells play an important regulatory role in the circulation as a physical barrier and as a source of a variety of regulatory substances. Endothelium-derived nitric oxide and prostacyclin are released in response to physical stimuli, hormones and platelet-derived substances and induce vascular relaxation and inhibition of platelet function. Certain substances can evoke a hyperpolarization of smooth muscle cells. In addition, endothelial cells can release several contracting factors (i.e. endothelin, thromboxane A2, angiotensin II, superoxide and unidentified endothelium-derived contracting factors), at least under certain conditions. Endothelial cells are also a source of growth inhibitors and promoters, such as heparin and heparin sulphates, platelet-derived growth factor and thrombospondin. Several vasoactive substances produced by the endothelium, such as nitric oxide, endothelin and angiotensin II may also play a role in the regulation of vascular growth. Thus, the endothelial layer can regulate vascular tone and growth. A dysfunction of these endothelium-dependent regulatory systems may play a role in cardiovascular diseases, such as hypertension and atherosclerosis.
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PMID:Endothelial control of vascular tone and growth. 220 57

The endothelium modulates coronary vascular tone by the release of endothelium-derived relaxing or contracting substances. The endothelium-derived relaxing factor has been identified as nitric oxide synthesized in endothelial cells from L-arginine. The endothelium can release other relaxing substances such as prostacyclin and a hyperpolarizing factor. Endothelin-1 is a potent vasoconstrictor peptide formed by endothelial cells, and is likely to be the physiologic antagonist of endothelium-derived relaxing factor. Other putative contracting factors include superoxide anions and products of arachidonic acid metabolism. Endothelium-derived relaxing factor is released spontaneously and in response to flow, platelet-derived products (that is, serotonin, thrombin and adenosine diphosphate) and certain autacoids (that is, acetylcholine, bradykinin, histamine, substance P, vasopressin, alpha-adrenergic agonists). A considerable heterogeneity of responses exists among vessels of different size from different anatomic origin and different species. Hypercholesterolemia, atherosclerosis, hypertension and myocardial ischemia or reperfusion, or both, impair endothelium-dependent relaxation. Under normal conditions, endothelium-derived relaxing factor appears to dominate the control of vascular tone of large and small coronary vessels, whereas in disease states, endothelium-derived contracting factors are released. Impairments of endothelial function may be important in the development of various forms of cardiovascular disease.
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PMID:Endothelial control of vascular tone in large and small coronary arteries. 240 18

This review addresses the question of whether platelet-derived serotonin locally released at the resistance vessel wall may contribute via selective 5-hydroxytryptamine (5-HT) receptors to vasoconstriction and whether this chain of events is enhanced with age and high blood pressure. In platelets from animals and humans, both age and hypertension are associated with greater shape change and aggregation responses, reduced serotonin uptake and content, and increased release. Removal of the endothelium, age, and high blood pressure enhance vasoconstrictor responses to serotonin. In the presence of endothelial damage and arteriosclerotic vascular disease, particularly with reduced blood flow in areas of stenosis, platelets may aggregate, resulting in high local 5-HT concentrations and 5-HT-induced vasoconstriction. Since alpha 1-adrenoceptor-mediated vasoconstriction is independent of age, the age-related antihypertensive efficacy of the 5-HT2-receptor antagonist ketanserin (with alpha 1-blocking property) helps to define pharmacologically 5-HT2-receptor-mediated platelet aggregatory and vasoconstrictor mechanisms. 5-HT2-receptor antagonists represent a new antihypertensive tool with the potential of reducing thromboembolic complications and vascular damage, particularly in older patients.
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PMID:Age and the platelet serotonin vasoconstrictor axis in essential hypertension. 245 12

Hypertension causes biochemical and morphological changes in the vessel wall by unknown mechanisms. Locally produced substances may have a role in mediating these vascular changes. We have studied the expression of platelet-derived growth factor (PDGF) B chain and PDGF A chain, insulin-like growth factor (IGF)-I and IGF-II, endothelial cell growth factor (ECGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta) in aortic tissue from normotensive rats and rats made hypertensive by deoxycorticosterone (DOC)/salt treatment. Using Northern blotting, we found that genes for each of these growth factors were transcriptionally active in the aorta of both normotensive and hypertensive rats. TGF-beta aortic mRNA levels increased up to threefold as a result of DOC/salt hypertension. In contrast, no major changes in the expression of either PDGF chain, IGF-I or II, ECGF, or bFGF were detectable. The results indicate that at least seven genes coding for growth factors that were shown previously to influence growth and function of vascular cells in vitro, are expressed in rat aorta in vivo. These findings support the hypothesis that synthesis and release of growth factors in the arterial wall are involved in autocrine and/or paracrine regulatory mechanisms. In addition, the increased expression of TGF-beta in vivo may have a role in mediating the aortic changes induced by hypertension.
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PMID:Growth factor expression in aorta of normotensive and hypertensive rats. 270 37

We investigated the association between low-density lipoprotein (LDL), triglycerides, and platelet activation in 18 patients with hypertension age 41-64 years and 18 with diabetes mellitus aged 43-70 years. Platelet P-selectin positivity and the microparticle level (indicators of activation) were both significantly higher in the diabetics than in healthy controls (P-selectin: 28.0% +/- 7.5% vs. 7.3% +/- 4.2%, P < 0.001; microparticles: 1900 +/- 966 vs. 526 +/- 158/10(4) platelets, P < 0.01). In contrast, there was no significant increase of either parameter in the patients with hypertension. Plasma microparticle levels were also significantly greater in the diabetics with high LDL levels than in those with low LDL levels (2375 +/- 949 vs. 1519 +/- 796/10(4) platelets, P < 0.05), and in those with high rather than low triglyceride levels (2188 +/- 845 vs. 1492 +/- 783/10(4) platelets, P < 0.05). However, platelet positivity for P-selectin was not significantly different between these two subgroups. Microparticle and P-selectin levels both showed no significant difference between the hypertensive patients with high and low LDL or triglyceride levels. These results suggest that platelet-derived microparticles may participate in the development or progression of atherosclerosis in patients with diabetes mellitus.
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PMID:Platelet-derived microparticles may influence the development of atherosclerosis in diabetes mellitus. 757 78


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