Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The spontaneously hypertensive rat (SHR)--animal model for human essential hypertension--develops a generalized arteriopathy. The present paper discusses the atherogenic influence of hypertensive arterial lesions. The following changes in the intima might influence its permeability and barrier function, increase the trapping effect and stimulate the smooth muscle cell proliferation: the hyper-reactivity of endothelial cells; the decreased thickness of endothelial cell periphery; the reduced intercellular junction pathways; the increase in basal lamina and glycosaminoglycan sub-endothelial material; the mononuclear cell infiltrations; the widened fenestrae in the internal elastic lamina. Some hypertensive changes of the tunica media may also interact with atherogenic process through reduced smooth muscle cell lipolytic capabilities, slowed transmural diffusion, perturbed efflux, aggravated media hypoxia, namely: the decrease in esterase and cholinesterase activities, the activations of some lysosomal enzymes, the increase in collagen, glycosaminoglycan and elastin content; the increased media thickness and transmural passage; the modified smooth muscle cell behavior.
 ...
PMID:[Hypertensive arteriopathy and atherogenesis: cellular and molecular interactions]. 310 95

The effects of chronic therapy, using an angiotensin converting enzyme (ACE) inhibitor (S9490-3 perindopril, 1 mg/kg), on the mechanical and structural properties of large arteries were studied in two-kidney, one clip (2K, 1C) Goldblatt hypertensive and spontaneously hypertensive rats (SHR) compared with matched normotensive Wistar and Wistar-Kyoto (WKY) animals. The treatment was carried out for 1 month in Goldblatt-hypertensive rats and 3 months in SHR, i.e. for 1 month after blood pressure was normalized. At the end of the treatment period the passive mechanical properties of the isolated carotid artery were measured in situ. Carotid compliance was calculated from the pressure-volume relationship between 50 and 250 mmHg. Morphological parameters of the aortic wall, including medial thickness, nucleus density and elastin and collagen content, were recorded by an automated morphometric system. Renal and essential hypertension were associated with a shift of the passive pressure-volume relationship in the carotid, corresponding to a decrease in arterial compliance. The passive mechanical properties of the carotid were normalized by ACE inhibitor treatment in renovascular hypertensive rats but remained unchanged in chronically treated SHR. The ACE inhibitor completely reversed the medial hypertrophy in Goldblatt-hypertensive rats but the reversal of medial hypertrophy was incomplete in SHR. The elastin to collagen ratio in the aortic media was significantly increased by 3 months of treatment with the ACE inhibitor in the SHR and WKY groups but remained unchanged in the Goldblatt-hypertensive and Wistar rats treated for 1 month.
 ...
PMID:Arterial effects of angiotensin converting enzyme inhibition in renovascular and spontaneously hypertensive rats. 322 86

Vessels of known position in the vascular tree of the kidneys of two cases with a long history of progressive systemic sclerosis--one normotensive, one hypertensive--were examined morphometrically. Medial thickness, intimal thickness and the relative content of collagen and elastin in the vascular media were measured. Smooth muscle nuclei were counted in the arterial cross section. These morphometric data were compared with those obtained from two autopsy cases--one with a history of essential hypertension, one without any hypertensive history. The findings suggest that progressive sclerosis induces intimal thickening in all branches of the renal artery down to a distented diameter of 200 microns. In the case where progressive sclerosis was complicated by arterial hypertension increased medial thicknesses were found, similar to the findings in the case with a history of essential hypertension.
 ...
PMID:Morphometry of intrarenal arteries in progressive sclerosis. 741 45

Increased resistance to blood flow in arteries is built up by blockade of transport of saturated fatty acids of triglycerides in VLDL to cell through apoE/B-100 receptor endocytosis (active transport). This way does not affect the structure of cell membrane. Blockade of the active transport stimulates the compensating activation of lipolysis increasing the level of free saturated fatty acids in the blood. These fatty acids are included into the cell membrane via passive transport. In the membrane fatty acids form local domains with unregulated permeability and nonspecific ion transport: Na+ and Ca2+ enter into cell without any control and K+ and Mg2+ leak out. Responding cells activate Na+, K(+)- and Ca(2+)-ATPase and cholesterol synthesis. Ion pumps activate Na+ and Ca2+ out-fluxes; cholesterol blocks nonspecific ion permeability, but increases membrane microviscosity and inhibits secondary activity of ion pumps, thus forming vicious circle of hypernatriemia and hypercalciemia disturbing functions of loose connective tissue. They increase cell size, promote synthesis and secretion of collagen and elastin. It has led to wail thickening, elasticity drop and artety clear cross section narrowing. The increase of sensitivity to contractility of smooth muscle cells, hyperreactivity towards pressor regulators and resistance to depressor regulators cause artery spasm, peripheral resistance increases and starts up pathogenesis of essential hypertension.
 ...
PMID:[Disruption of saturated fatty acids in cells in the pathogenesis of essential hypertension]. 984 18

Mechanical properties of arteries are altered in some rat models of hypertension, and this may influence peripheral resistance and blood pressure as well as some of the complications of hypertension. It has usually been assumed that arterial wall stiffness is increased in hypertension, although recent studies suggest that this may not necessarily be the case in large arteries. We determined whether the mechanics of human resistance arteries are altered in hypertension. Subcutaneous resistance arteries (lumen diameter<300 microm) were isolated from hypertensive and normotensive subjects of similar ages (46+/-3 and 43+/-4 years, respectively). Vessels were mounted in a pressurized myograph, deactivated, and exposed to intraluminal pressures ranging from 3 to 140 mm Hg. At each pressure, lumen and media dimensions were measured. Media-to-lumen ratio and media width were greater in hypertensive vessels, reducing wall stress (P<0.01), whereas media cross section was similar in vessels from both groups. Isobaric elastic modulus (which is influenced by vessel geometry and by wall component stiffness) was lower in hypertensive vessels (P<0. 01). Stiffness of wall components (slope of incremental elastic modulus versus stress, which is geometry-independent) was significantly lower in hypertensive vessels (8.2+/-0.7) versus normotensive vessels (11.0+/-1.0, P<0.05), whereas distensibility was unchanged. Electron microscopic analysis of the media of the small arteries showed a greater collagen to elastin ratio (P<0.05) in the media of vessels from hypertensive patients. In conclusion, the stiffness of wall components (slope of elastic modulus versus stress) is not increased but is in fact decreased in subcutaneous resistance arteries from patients with mild essential hypertension. Reduced stiffness of resistance arteries from hypertensive patients does not appear to relate to changes in volume density of extracellular matrix components but may be the result of changes in extracellular matrix architecture or cell-matrix attachment, which remains to be established.
 ...
PMID:Mechanics and composition of human subcutaneous resistance arteries in essential hypertension. 993 Nov 67

The objective of the present study was to determine the viscoelastic properties of the common carotid artery in 35 patients with aortic aneurysm before surgery (AAA) (age 71 years, range 61-84), in comparison with 48 patients with essential hypertension (HT: 50 years, range 24-88) and 44 normotensive subjects (NT: 44 years, range 23-85). The second objective was to establish the relations between common carotid artery (CCA) viscoelastic properties and histologic lesions observed on AAA segments, obtained after surgery. CCA diameter was larger and distensibility smaller in AAA patients than in HT and NT. Distensibility of the aortic aneurysm was smaller than that of upstream 'normal' aorta, itself being smaller than control aortas. AAA wall lesions were extensive, associating adventitial and medial fibrosis, elastolysis, smooth muscle rarefaction, neovascularization, inflammation and plaques. The grade of these lesions was not correlated with the mechanical properties of the aorta and CCA; however, they could explain their qualitative alterations. AAA is characterized by severe stiffening and dilatation of large arteries distant from the aneurysm location. Whether this pattern of arterial phenotype is explained by the increase in stiff material (collagen) and the rarefaction of distensible material (smooth muscle and elastin) remains to be determined.
 ...
PMID:[Associations between viscoelastic properties of large arteries and their extracellular matrix composition in abdominal aortic aneurysms in humans]. 1021 30

Etiopathogenesis of arterial hypertension and coronary disease involves interaction of numerous exogenous factors which determine the clinical course and therapeutic response in genetically predisposed individuals. The role of numerous cardiovascular risk factors has been reevaluated during the past few years, yet some unresolved issues and gaps still remain. One of the still insufficiently studied factors is lipoprotein (a) [Lp (a)] which belongs to a subclass of LDL lipoproteins. Its important component is apolipoprotein (a) which is structurally similar to plasminogen. This characteristic can be followed through evolution and is probably crucial for its physiologic but also pathophysiologic role. Actually, through its competition with plasminogen, Lp (a) interferes with the process of fibrinolysis and may contribute to tissue healing and restoration but also support and accelerate atherothrombotic process. Lp (a) concentration is stable and genetically determined in an individual and the indication that persons with elevated levels are permanently exposed to increased risk is supported by the data on twofold incidence of myocardial infarction in mothers of children with highest Lp (a) concentrations. Apart from competing with plasminogen via apolipoprotein (a), Lp (a) increases the activity of inhibitors of plasminogen-I activator and reduces the activity of transforming growth factor-beta. This results both in the absence of fibrinolysis and promotion of migration and proliferation of media smooth muscle cells, which are important in the onset of atherosclerotic process. Lp (a) binds to elastin via apolipoprotein B, resulting in oxidation and facilitated entry into macrophages and their transition into the so-called foam cells, also an important sign of early atherosclerosis. Although many pathophysiologic processes by which Lp (a) contributes to atherosclerosis have also been confirmed by animal experiments as well as by the presence of histologic evidence, clinical significance of elevated Lp (a) concentration is still questionable. However, results of prospective studies and metaanalyses were published few months ago and identified decisively Lp (a) as a factor that increases cardiovascular risk primarily in patients in whom other risk factors were also present. According to currently prevailing attitude, routine determination of Lp (a) is not justified and, according to most authors, its determination is useful in patients who had a cardiovascular incident at the age under 55 years, in those with recurrent coronary stenosis, or those with positive family history of such incidents. As Lp (a) is genetically determined, its detection in the early stages of essential hypertension might be a useful prognostic marker but a period of observation is still necessary for correct selection of hypertensive patients. Apart from the observation that hormone replacement therapy significantly decreases the Lp (a) level, there is currently no information on the effectiveness of either dietary or drug therapy. Due to Lp (a) antifibrotic effects, small aspirin doses may be beneficial to these patients, as well as B complex vitamins since hyperhomocysteinemia enhances atherogenicity of Lp (a). Therapeutic approach to patient with increased Lp (a) levels is currently based on as strict regulation of arterial pressure, glycemia and other dislipidemias as possible. In the present clinical practice, the elevated level of this lipoprotein indicates a patients with elevated cardiovascular risk, regardless of the fact whether Lp (a) is only a marker or an active factor of pathophysiologic process. Increased Lp (a) concentration may refer to the need for therapy, frequent monitoring and determination of even stricter aims for these individuals by selecting metabolically neutral and best tolerated drugs.
 ...
PMID:[Lipoprotein (a)--a mysterious factor in atherogenesis]. 1267 78

Mice haploinsufficient for elastin develop structural changes in vessel walls similar to those seen in patients with mutations in the elastin gene. A new study demonstrates that due to mechanical changes in the vessel wall, these animals exhibit increased mean arterial pressures. The results evoke the possibility that alterations in elastin may contribute to the development of essential hypertension in patients.
 ...
PMID:Decreased elastin in vessel walls puts the pressure on. 1459 67

Supravalvular aortic stenosis is an autosomal-dominant disease of elastin (Eln) insufficiency caused by loss-of-function mutations or gene deletion. Recently, we have modeled this disease in mice (Eln+/-) and found that Eln haploinsufficiency results in unexpected changes in cardiovascular hemodynamics and arterial wall structure. Eln+/- animals were found to be stably hypertensive from birth, with a mean arterial pressure 25-30 mmHg higher than their wild-type counterparts. The animals have only moderate cardiac hypertrophy and live a normal life span with no overt signs of degenerative vascular disease. Examination of arterial mechanical properties showed that the inner diameters of Eln+/- arteries were generally smaller than wild-type arteries at any given intravascular pressure. Because the Eln+/- mouse is hypertensive, however, the effective arterial working diameter is comparable to that of the normotensive wild-type animal. Physiological studies indicate a role for the renin-angiotensin system in maintaining the hypertensive state. The association of hypertension with elastin haploinsufficiency in humans and mice strongly suggests that elastin and other proteins of the elastic fiber should be considered as causal genes for essential hypertension.
 ...
PMID:Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency. 1459 55

Atherosclerosis is characterized by inflammatory metabolic change with lipid accumulation in the artery. Atherosclerotic plaque occurs at discrete locations in the arterial system and involves the proliferation of smooth muscle cells (SMCs) together with imbalance of the extracellular matrix elements, elastic fiber in particular. The role of elastin in arterial development and disease was confirmed by generating mice that lack elastin. Thus, elastin is a critical regulatory molecule that regulates the phenotypic modulation, proliferation and migration of SMCs. We estimated that elastin expression and SMC proliferation are coupled inversely: potent stimulators of cell proliferation may potentially inhibit elastin expression and potent inhibitors of cell proliferation can stimulate elastin expression. Moreover, elastin was found to be expressed maximally at the G(0) and minimally at the G(2)/M phase during the cell cycle, suggesting that its expression is regulated by the cell growth state. The elastin peptide VPGVG enhanced SMC proliferation, resulting in the reduction of elastin expression. The inhibition of elastin expression by elastin fragments may be reflected in the negative feedback regulatory mechanism. The relationship between cell proliferation and elastin expression may be changed in atherosclerosis. Areas of atherosclerotic plaque show abnormality of elasticity and permeability from the viewpoint of the physiological function of the arterial wall. The etiology was estimated to be that cholesterol and calcium are deposited on the elastic fiber, resulting in decreased elastin synthesis and cross-linking formation. In addition, these dysfunctions of elastin fiber are also associated, in that the down-regulation of elastin and its related components (fibrillin-1 and lysyl oxidase) are directly related to calcification in SMCs. The denatured arterial elastin by cholesterol and calcium accumulation was also susceptible to proteolytic enzymes such as elastase and matrix metalloproteinase (MMP). Therefore, metabolic change in elastic fiber induces decreased elasticity and is associated with essential hypertension. Vitamin K(2) is used in drug therapy against atherosclerosis, or calcification in diabetes mellitus or dialysis, due to its promotion of the carboxylation of the matrix Gla protein.
 ...
PMID:Atherosclerosis and matrix dystrophy. 1555 5


1 2 Next >>