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

The pregnancy disorder preeclampsia continues as a major cause of maternal and infant mortality and morbidity. Despite intensive research since its recognition 100 years ago, our lack of understanding is evidenced by therapy which remains empiric, early delivery. Part of our failure to more completely understand the syndrome is due to excessive attention to the blood pressure elevation which accompanies the disorder, to the exclusion of a panoply of other physiologic aberrations. Although hypertension, if markedly elevated, can lead to maternal morbidity, it is not usually an important contributor to the pathophysiology of preeclampsia. It is primarily important as a marker for vasoconstriction, which in association with activation of coagulation reduces perfusion to many organs, including the fetal-placental unit. The earliest and likely most important pathophysiologic change is reduced placental perfusion secondary to abnormal implantation and/or a relative increase in placental mass. We propose that reduced placental perfusion results in the production of agent(s) by this organ, which injures or activates endothelial cells. The resulting endothelial cell dysfunction increases sensitivity to normal endogenous pressors, activates the coagulation cascade, and increases vascular permeability. These changes produce the characteristic pathophysiologic changes of the disorder. Evidence supporting this hypothesis includes abnormal endothelial morphology long recognized in glomerular capillaries, increased circulating fibronectin, and increased plasma mitogenic activity that long antedates the clinical disorder. In addition, an agent(s) is present in the blood of these women which activates endothelial cells in vitro as evidenced by increased release of [51Cr] chromium and increased production of PDGF. Preeclampsia is clearly more than "pregnancy induced hypertension."
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PMID:Clinical and biochemical evidence of endothelial cell dysfunction in the pregnancy syndrome preeclampsia. 193 Aug 53

Current concepts of the pathogenesis of preeclampsia involve the generalized dysfunction of maternal vascular endothelial cells. We measured the endothelial isoform of fibronectin as a marker of endothelial cell injury throughout pregnancy in a prospective, case-control study. Nineteen women met strict criteria for the diagnosis of preeclampsia. Nineteen normal pregnant women, and 19 women with gestational hypertension but without other stigmata of preeclampsia (transient hypertension) were selected from the same cohort and matched according to race, age, nulliparity, and gestational age at delivery. Plasma levels of cellular fibronectin were significantly elevated in women meeting strict clinical and biochemical criteria for preeclampsia but not in women with normal pregnancies or transient hypertension. Moderate but significant elevations in mean levels were found in the second trimester in women destined to have preeclampsia, as compared with matched normal and transient hypertension groups (p less than 0.05). The results indicate that elevated plasma levels of cellular fibronectin are not simply the result of increased blood pressure but reflect a maternal insult specific to the syndrome of preeclampsia. Elevation of the mean concentration during the midtrimester is consistent with the hypothesis that endothelial cell injury is a specific lesion that occurs early in the course of preeclampsia, before clinical signs and symptoms.
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PMID:High plasma cellular fibronectin levels correlate with biochemical and clinical features of preeclampsia but cannot be attributed to hypertension alone. 195 50

Plasma fibronectin (Fn) levels and activities of antithrombin III (AT-III) function were determined in 219 cases, including 61 cases of pregnancy-induced hypertension (PIH) and 127 normal pregnant women and 31 normal nonpregnant women as controls. The plasma Fn levels of PIH patients were significantly increases to 539.04 +/- 256.3 mg/L, while the plasma AT-III activities were significantly lowered to 76.1 + 13.9%. There was a negative correlation between plasma Fn and AT-III in PIH patients (r = -0.377, P less than 0.01). High plasma Fn and low plasma AT-III in PIH were related to proteinuria. Plasma AT-III decreased as PIH became more severe. The results suggested that the high plasma Fn with low AT-III levels may serve as an indicator of the severity of PIH.
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PMID:[Changes of plasma fibronectin and antithrombin III in pregnancy-induced hypertension]. 200 75

In chronic models of hypertension such as the spontaneously hypertensive rat (SHR), thickening of the media of large arteries occurs mainly through smooth muscle cell (SMC) hypertrophy accompanied by DNA replication resulting in large polyploid cells. In resistance vessels of SHR, medial hypertrophy occurs through a hyperplastic response. It has been suggested that this hyperplasia is due to mitogens such as platelet-derived growth factor (PDGF), while the hypertrophied polyploid cells occur from stimulation by angiotensin II from within the vessel wall. Angiotensin II activates many of the same cellular pathways as PDGF, including stimulation of phospholipase C, mobilization of intracellular calcium and activation of Na+/H+ exchange. Both induce transient increases in the proto-oncogenes c-fos and c-myc. However, a possible explanation for the difference in SMC response may be involvement of an intracellular pathway stimulated by PDGF (but not by angiotensin II), such as stimulation of JE (a cytokine-like molecule), which may activate transcriptional events necessary for mitogenesis. In atherosclerosis vascular hypertrophy occurs in the form of focal intimal thickening and results from hyperplasia of diploid SMC and their greatly increased production of extracellular matrix, (particularly collagen) and the accumulation of intra- and extracellular lipid. The SMC involved in atherogenesis are phenotypically modified compared with the SMC of undiseased regions, and amongst other features have a lower volume fraction of myofilaments (Vvmyo). Associated with modulation to a low Vvmyo are increases in SMC expression of mRNA for collagens type I (alpha 1 and alpha 2) and type III (alpha 1), elastin, fibronectin, as well as massive increases in collagen protein (26- to 45-fold), glycosaminoglycans (5-fold), and lipid accumulation (7-fold).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of vascular hypertrophy. 203 94

Interactions between extracellular fibronectin and vascular cells are thought to influence the phenotype of those cells. To determine if changes in fibronectin expression accompany the phenotypic changes of vascular tissue characteristic of experimental hypertension, steady state mRNA levels for fibronectin were determined in aortae of normotensive and hypertensive rats. A 3-6-fold increase in fibronectin mRNA was observed in aortic tissue of hypertensive rats following 3 weeks of treatment with deoxycorticosterone and salt, whereas if rats were treated only with deoxycorticosterone or salt alone, no changes occurred. The changes were reversed by normalization of blood pressure. The increases observed were localized to aorta and not to the periaortic tissue. Angiotensin II infusion using osmotic minipumps also caused an increase in fibronectin expression. Age-dependent increases in aortic fibronectin mRNA occurred in several rat strains, and the combined effects of hypertension and aging were greater than either variable alone. A clear distinction between the expression of fibronectin mRNA and that for collagen or tropoelastin were found in hypertensive and aging models. Aortic fibronectin was also increased in the hypertensive rats as determined by Western blot analysis. The findings indicate that elevation in blood pressure increases fibronectin expression in rat aorta and suggest that such changes may influence the aortic cellular responses to hypertension.
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PMID:Effect of hypertension on fibronectin expression in the rat aorta. 225 39

Forty-five women with preeclampsia and 39 woman with chronic hypertension in pregnancy were studied by catheterization of the superior vena cava and by impedance cardiography before therapy was started. An initial hemorrheology and hemostaseologic protocol was prepared which included hematocrit, erythrocyte aggregation, erythrocyte deformability, plasma viscosity, colloid osmotic pressure, serum osmolality, uric acid, fibronectin, antithrombin III and fibrinogen. The hematocrit and the peripheral resistance were greater in preeclampsia than in essential hypertension. Moreover, preeclamptic patients showed a significantly lower cardiac output and central venous pressure than women with chronic hypertension. On the other hand, the plasma viscosity of women with essential hypertension increased, whereas patients with preeclampsia showed a lower erythrocyte deformability and a higher concentration of leukocytes. Finally, volume expansion with Hydroxyethyl-starch appears to be of therapeutic benefit for hypertensive patients with low cardiac output.
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PMID:[Hemodynamic and hemorheologic findings in patients with pregnancy-induced hypertension: comparison of pre-eclampsia and chronic hypertension]. 237 51

We have studied the effect of dietary supplementation with 4 g of n-3 polyunsaturated fatty acids (n-3 PUFA) daily for 6 wk on plasma lipids, haemostasis and monocyte chemotaxis in 10 patients with untreated hypertension. Total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides did not change, but the ratio of total to HDL-cholesterol was significantly reduced after the fish oil supplement. Platelet function was unaltered by intake of n-3. Plasma fibrinogen and fibronectin decreased after supplementation with n-3 PUFA, while the effects on fibrinolysis were equivocal. Monocyte chemotaxis was reduced by the supplement. These data lend support to a role for an increased intake of n-3 PUFA in the management of patients with hypertension.
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PMID:The effect of n-3 polyunsaturated fatty acids on lipids, platelet function, coagulation, fibrinolysis and monocyte chemotaxis in patients with hypertension. 238 18

We studied parameters of hemostasis reported to be altered with "pure" preeclampsia in hypertensive disorders of pregnancy. Plasma fibronectin, antithrombin, and alpha-2 antiplasmin were measured in normal pregnancies (N = 26) and in pregnancies complicated by preeclampsia (N = 19), hypertension (N = 11), and chronic hypertension with superimposed preeclampsia (N = 11). Preeclampsia, both pure and superimposed, was associated with high fibronectin (P less than .001), low antithrombin III (P less than .001), and low alpha-2 antiplasmin (P less than .05) levels, suggesting endothelial injury, clotting, and fibrinolysis, respectively. Alpha-2 antiplasmin was increased with chronic hypertension (P less than .001), regardless of whether there was superimposed preeclampsia. Fibronectin appeared to be more closely linked with preeclampsia than antithrombin III or alpha-2 antiplasmin and may prove valuable in detecting preeclampsia when evaluating hypertension in pregnancy.
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PMID:Hemostasis in hypertensive disorders of pregnancy. 245 98

Blood pressure, proteinuria, and plasma fibronectin and plasminogen activator inhibitor-1 levels were measured in 120 apparently healthy normotensive primigravid women during the first, second, and third trimesters of pregnancy and 2 days post partum. Thirty-two women developed hypertension (diastolic blood pressure greater than or equal to 90 mm Hg) that in 17 women was associated with proteinuria (greater than 0.3 gm/day). Fibronectin levels were 83% +/- 22% of normal (mean +/- SD) during the first trimester and 75% +/- 20% at term in the healthy women but increased from 94% +/- 36% to 187% +/- 36% in the women who developed gestational hypertension (with or without proteinuria) (p less than 0.0001). Plasminogen activator inhibitor-1 levels increased from 26 +/- 19 ng/ml to 110 +/- 86 ng/ml in healthy women and from 32 +/- 35 ng/ml to 290 +/- 90 ng/ml in hypertensive women (p less than 0.001). Increased levels of fibronectin at 25 to 36 weeks of pregnancy (greater than or equal to mean + 2 SD of the healthy women, or greater than 140%) were found in 31 of the 32 women with gestational hypertension with or without proteinuria and in 5 of the 88 healthy women (sensitivity 96%, specificity 94%). Fibronectin levels increased 3.6 +/- 1.9 weeks earlier than the onset of hypertension and/or proteinuria. Increased levels of plasminogen activator inhibitor-1 at 25 to 32 weeks (greater than or equal to 280 ng/ml) were found in 16 of the 32 women who developed gestational hypertension with or without proteinuria and in 4 of the 88 healthy women (sensitivity 50%, specificity 95%). We conclude that increased fibronectin levels are the best predictor of gestational hypertension with or without proteinuria and that its level in plasma increases several weeks before the development of hypertension.
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PMID:Predictive value of increased plasma levels of fibronectin in gestational hypertension. 250 45

Plasma fibronectin concentration was determined by immuno-nephelometer analysis in 316 pregnant women between 22 and 38 weeks. The plasma fibronectin concentration increases progressively during normal pregnancy. From 22 to 30 weeks, the 90th percentile is 350 mg/l, and from 30 to 38 weeks it is 400 mg/l. 29 patients had a fibronectin level greater than 400 mg/l. Of this group, 95% of the creatinine's clearance were significantly lowered. From 30 weeks of gestation, the correlation between an elevated level of fibronectin and the development of hypertension is 100%. Our results confirm that this glycoprotein may be an early indicator of preeclampsia.
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PMID:[Fibronectin: an early marker of pre-eclampsia]. 261 26


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