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

Hypertension is a risk factor for the development of atherosclerosis, although the mechanisms have not been well elucidated. As the cellular and molecular mechanisms of the pathogenesis of atherosclerosis and the effects of hypertension are being more clearly defined, it becomes apparent that the two processes have certain common mechanisms. The endothelium is a likely central focus for the effect of both diseases. There is increasing evidence that atherosclerosis should be viewed fundamentally as an inflammatory disease. Atherogenic stimuli such as hyperlipidemia appear to active the inflammatory response by causing expression of mononuclear leukocyte recruiting mechanisms. The gene for one of these, the vascular cell adhesion molecule-1, is controlled at least in part by transcriptional factors regulated by oxidative stress, which modifies the redox state of the endothelial cell. Alterations in the redox state of the arterial wall also may contribute to vascular smooth muscle cell growth. In a somewhat parallel fashion, there is evidence that hypertension may also exert oxidative stress on the arterial wall. This article reviews evidence that leads to the postulate that hypertension predisposes to and accelerates atherosclerosis at least in part because of synergy between elevated blood pressure and other atherogenic stimuli to induce oxidative stress on the arterial wall.
Hypertension 1995 Feb
PMID:Theodore Cooper Memorial Lecture. Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective. 784 63

To characterize alterations of renal vessels occurring during systemic hypertension elicited in rats by 5, 10, and 25 days of treatment by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME)(20 mg/kg daily), preglomerular vasculatures, consisting of arcuate arteries and their branches, interlobular arteries, and afferent arterioles, were isolated by HCl maceration. Blockade of nitric oxide synthase significantly increased tail-cuff systolic blood pressure by 21 +/- 2% and 42 +/- 3% after 5 and 25 days, respectively. Medias of hypertensive arcuate arterial branches and interlobular arteries but not of afferent arterioles had focal deposits of Sudan black-positive lipid droplets. At 25 days, vessel wall thickness increased by 72 +/- 6% along the sudanophilic areas. Immunostaining of sudanophilic lesions with a panel of antibodies unveiled medial cell proliferation, macrophage invasion, immunoreactive vascular cell adhesion molecule-1, and low-density lipoprotein. The frequency of sudanophilic lesions increased with time to affect 26 +/- 2% and 36 +/- 3% of arcuate arterial branches and interlobular arteries, respectively, at 25 days. Hypertensive L-NAME-treated rats developed glomerular injury probed by albuminuria and glomerular immunostaining for alpha-smooth muscle actin. Administration of the nonselective endothelin antagonist bosentan (30 mg/kg daily) blunted the development of sudanophilic lesions during L-NAME treatment without affecting arterial hypertension or degree of glomerular injury. Therefore, L-NAME hypertension leads to rapid development of focal, inflammatory, proliferative, and sudanophilic lesions along preglomerular vessels, suggesting atherosclerosis-like processes. Furthermore, endothelin is a likely mediator in the development of these lesions.
Hypertension 1996 Mar
PMID:Preglomerular sudanophilia in L-NAME hypertensive rats: involvement of endothelin. 869 42

Angiotensin II (AII) is recognized as being an important factor in the pathogenesis of hypertension and atherosclerosis. Monocyte binding to affected endothelial cells is one of the earliest features of atherosclerosis. However, the effect of AII on monocyte binding has not been fully studied. Treatment of human aortic endothelial cells (HAEC) and rabbit aortic endothelial cells (RAEC) for 18 hours with AII induced the adhesion of monocytes but not neutrophils to these cells. This induction was reduced by inhibitors of AII receptors (Type I and Type II). Angiotensin II-induced monocyte binding was not associated with induction of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), or intercellular adhesion molecule-1 (ICAM-1). These results suggest that AII can accelerate the rate of atherosclerosis by increasing monocyte binding to the endothelium.
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PMID:Angiotensin II increases monocyte binding to endothelial cells. 883 2

Secondary prevention of atherosclerosis, especially before the onset of symptoms, appears desirable and could be possible with a serum marker detecting atherosclerosis. Circulating, shedded forms of adhesion molecules may serve as such because their expression is upregulated in atherosclerotic plaques. In 52 patients with peripheral arterial vascular disease (Fontaine class IIa, 7 patients; class IIb, 29 patients; and class III, 16 patients), the extent of atherosclerosis was evaluated on the basis of angiograms of a large portion of the arterial system. The area diseased by atherosclerosis was determined by the percentage of vessel wall irregularities of the following calculated segments: aorta (distal from the kidney arteries), common iliac artery, external iliac artery, common femoral artery, lateral circumflex femoral artery, and popliteal artery. The maximal surface area that could exhibit atherosclerotic changes was 250 cm2. The serum concentration of circulating vascular cell adhesion molecule-1 (VCAM-1) correlated with the extent of atherosclerosis (r = .8, P < .001). In contrast, circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin (as markers for endothelial cell damage) did not correlate with the extent of atherosclerosis. Furthermore, circulating VCAM-1 could be used to indicate stages of atherosclerosis with a high degree of statistical significance. The potential bias of factors such as age, diabetes mellitus, hypercholesterolemia, arterial hypertension, renal failure, and history of myocardial infarction on the correlation of circulating VCAM-1 with the extent of atherosclerosis could be excluded by multivariate analysis. These findings suggest an important role of VCAM-1 in atherosclerosis and may serve as the basis for further evaluation of circulating VCAM-1 as a potential serum marker for atherosclerosis.
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PMID:Circulating vascular cell adhesion molecule-1 correlates with the extent of human atherosclerosis in contrast to circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin. 910 69

Several experimental studies suggest many similarities between the effects of hypertension and hypercholesterolemia on the arterial wall. Both hypertension and hypercholesterolemia have proinflammatory effects on the artery. An increased production of oxygen-free radicals leads to increased transcription of redox-sensitive genes, which increases the expression of vascular cell adhesion molecule-1 (VCAM-1) in the endothelium, resulting in increased recruitment of monocytes to the endothelium. The oxidative stress on the arterial wall may occur in both hypertension and hypercholesterolemia, therefore a synergistic reaction between hypertension and hypercholesterolemia may play a role in the atherosclerotic process as common causal mechanisms. Among therapeutic strategies to protect the vascular injury in both hypertensive and hypercholesterolemic state, future research should include direct attack on these common mechanisms.
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PMID:[Exacerbation of atherosclerosis induced by hypertensive and hypercholesterolemic states--potential mechanisms and therapeutic implications]. 928 30

In patients with essential hypertension, elevated soluble E-selectin (sE-selectin) levels may indicate endothelial cell injury or activation. We therefore sought to ascertain whether arterial blood pressure increased by the cold pressor test can modify serum concentrations of sE-selectin and other soluble forms of adhesion molecules, such as soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), or the expression of any adhesion molecules in circulating monocytes and lymphocytes. Our findings show that levels of sE-selectin, sVCAM-1, and sICAM-1 are higher in patients with essential hypertension than in normotensive subjects (sICAM-1, 380 +/- 52 versus 262 +/- 96 ng/mL, P<.05; sVCAM-1, 720 +/- 52 versus 625 +/- 38 ng/mL, P<.05; and sE-selectin, 75 +/- 21 versus 61 +/- 22 ng/mL, P<.05). Furthermore, in normotensive and hypertensive patients, the cold pressor test caused an increase in serum concentrations of sICAM-1, sVCAM-1, and sE-selectin, but it did not cause changes in the expression of adhesion molecules in circulating monocytes and lymphocytes. High arterial blood pressure may therefore increase the production of serum adhesion molecules, probably through endothelial activation.
Hypertension 1997 Oct
PMID:Cold pressor test raises serum concentrations of ICAM-1, VCAM-1, and E-selectin in normotensive and hypertensive patients. 933 82

In health, the vascular endothelium forms a multifunctional interface between the circulating blood and various tissues and organs of the body. It constitutes a selectively permeable barrier for macromolecules, as well as a nonthrombogenic and nonadhesive container that actively maintains the fluidity of blood. It is a metabolically active endocrine organ, serving as the source of multiple factors and mediators that are critical for normal homeostasis. These include vasodilators (nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor), vasoconstrictors (endothelin-1, thromboxane A2, prostaglandin H2 and components of the renin angiotensin system), various pro- and antithrombotic factors (e.g. tissue factor, platelet activating factor--PAF, von Willebrand factor), fibrinolytic activators and inhibitors (e.g. tissue plasminogen activator, plasminogen activator inhibitor-1), potent arachidonate metabolites (prostanoids), leukocyte adhesion molecules (e.g. E-selectin, P-selectin, intercellular adhesion molecule-1--ICAM-1, vascular cell adhesion molecule-1--VCAM-1), and multiple cytokines with activities of growth stimulators and inhibitors, transforming growth factors, proinflammatory and antiinflammatory mediators, tumour necrosis factors and chemotactic factors (chemokines). Besides these essential activities controlling the cardiovascular system, the endothelial cells represent an important part of the immune system as well. They have a pivotal role in the initiation and development of defensive and damaging inflammatory responses. Therefore endothelium can be considered as being the central equipment for the mutual exchange of life important information between the cardiovascular and immune systems. This in turn is leading to rapid advances in understanding the pathogenesis of some of the most serious and most common diseases, including inflammation, atherosclerosis and hypertension. (Tab. 7, Ref. 89.)
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PMID:[Vascular endothelium as a factor in information transfer between the cardiovascular and immune systems]. 958 73

Plasma concentrations of the circulating adhesion molecules ICAM-1 (CD54), VCAM-1 (CD106) were determined in 31 women with pre-eclampsia, 9 women with HELLP syndrome, and 13 women with transient pregnancy induced hypertension (PIH). Data were compared with a control group of 157 healthy pregnant women of the same gestational age. Furthermore, concentrations of circulating E-selectin (CD62E), P-selectin (CD62P), and PECAM-1 (CD31) were determined in a subpopulation of 17 women with pre-eclampsia. Plasma concentrations of circulating ICAM-1, VCAM-1, E-selectin, and PECAM-1 were significantly elevated in women with pre-eclampsia compared to healthy control pregnant women. Circulating ICAM-1 and VCAM-1 levels were also significantly elevated in the pre-eclampsia group compared to women with PIH. Concentrations of circulating P-selectin varied strongly in all experimental groups (SD > 70% of the mean), most likely reflecting various degrees of thrombocyte degranulation in the individual samples. Finally, longitudinal profiles of cICAM-1 and cVCAM-1 concentrations were determined in 123 healthy pregnant women between the 16th and the 42nd week of gestation. This analysis identified cICAM-1 and cVCAM-1 as tightly regulated plasma parameters that varied in a small concentration range. Concentrations of cICAM-1 and cVCAM-1 did not vary during pregnancy and the determined concentrations corresponded to the reported reference levels of nonpregnant individuals.
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PMID:[Soluble adhesion molecules in patients with pre-eclampsia]. 965 98

The purpose of this study was to investigate the relationship between complications arising from silent cerebral infarction (SCI) and changes in the levels of serum-soluble adhesion molecules in 82 elderly diabetic patients aged 60 years and older. SCI was found in 43 % of the 82 patients, with incidence increasing in relation to age. The prevalence of SCI was higher in subjects with hypertension, poor metabolic control and increased fibrinolysis. The levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) were higher in diabetic patients than in non-diabetic subjects (p < 0.05, p < 0.001, and p < 0.05, respectively). Also, sICAM-1 and sVCAM-1 were found at increased levels in diabetic patients with SCI compared to those without SCI (p < 0.01 and p < 0.05, respectively). In particular, the level of sICAM-1 was increased in patients with SCI due to perforating arterial occlusion, while the level of sVCAM-1 was increased in patients with SCI due to cortical arterial occlusion. However, no significant difference was found in sE-selectin levels. Overall average of the intima and media thickness (IMT) of the common carotid arteries increased with age. IMT proved to be greater in patients with SCI than in patients without SCI (p < 0.05), and showed a weak but significant positive correlation with sVCAM-1, while no correlation was found with either sICAM-1 or sE-selectin levels. In conclusion, measurement of serum adhesion molecules may be useful for diagnosing the early stages of brain damage and for prophylactic treatment which may prevent the onset or progression of SCI.
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PMID:The incidence and characteristics of silent cerebral infarction in elderly diabetic patients: association with serum-soluble adhesion molecules. 972 93

Chronic blockade of NO production induces hypertension and early occlusive and fibrotic end-stage organ damage owing to vascular lesions in the brain, kidney, and heart. In this study, we evaluated the inflammatory phenotypic changes induced in the arterial wall by chronic N(G)-nitro-L-arginine methyl ester (L-NAME) administration and the effect of an angiotensin II receptor (AT1) antagonist, irbesartan, on these changes. For this purpose, 2 groups of rats received L-NAME in the drinking water (50 mg x kg(-1) x d(-1)) for 2 months. One group received no other treatment and the other was treated with irbesartan (10 mg x kg(-1) x d(-1)). A third group (controls) received neither L-NAME nor irbesartan. After 8 weeks, plasma, aortas, and left ventricles were sampled from all 3 groups. Expression of inducible NO synthase (iNOS) was evaluated at both the mRNA (quantitative reverse transcription-polymerase chain reaction) and the protein (Western blot and immunohistochemistry) level in the aorta. Expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was evaluated by reverse transcription-polymerase chain reaction, Western immunoblotting, and immunohistochemistry; inflammatory cell infiltration by immunohistochemistry; and fibrosis by Sirius red staining. Chronic L-NAME administration induced the expression of iNOS in the aorta, which was localized in smooth muscle cells as shown by immunohistochemistry and NADPH diaphorase activity. ICAM-1 and VCAM-1 expression was also increased in aortas of L-NAME-treated rats. These phenotypic changes of the vascular wall were associated with inflammatory cell infiltration and fibrosis in the heart. All of these pathological phenomena were prevented by the angiotensin II antagonist irbesartan. The proinflammatory phenotypic changes of the vascular wall induced by blockade of NOS activity could be involved in the interaction between endothelial dysfunction and the development of arteriosclerosis.
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PMID:Chronic blockade of NO synthase activity induces a proinflammatory phenotype in the arterial wall: prevention by angiotensin II antagonism. 974 29


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