Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension and ageing are associated with decreased arterial compliance, increased thickening of the arterial wall, hypertrophy of arterial smooth muscle cells and an increase in the collagen content of the arterial wall. Increased blood pressure has been implicated as a causative factor in such adaptive vascular alterations, however, other factors, including angiotensin II and epidermal growth factor also induce one or more of these adaptations. Long term use of the angiotensin-converting enzyme (ACE) inhibitor perindopril 1 mg/kg has been shown to reduce blood pressure in spontaneous and renovascular hypertensive rats. Associated with this antihypertensive effect, perindopril completely reversed aortic medial thickening, increased arterial compliance (by 42%) and decreased aortic smooth muscle cell nucleus density (by 13%), but had no significant effect on the elastin: collagen ratio of the arterial wall. In contrast, in spontaneously hypertensive animals, perindopril partially reversed aortic medial thickening and had no significant effect on arterial compliance, despite significantly increasing the arterial wall elastin: collagen ratio in this experimental group. The effect of ACE inhibition appears to directly reflect the role of angiotensin II in the pathogenesis of different hypertensive states.
 ...
PMID:Vascular effects of ACE inhibition by perindopril. 240 91

Evidence is summarized that some structural changes in resistance arteries (hyperplasia of smooth muscle and others) precede the development of vessel changes in genetic hypertension. Additional changes, such as hypertrophy of vascular muscle and altered collagen and elastin, accompany hypertension and contribute to its maintenance. Furthermore, some membrane defects, including reduced Ca2+-pumping by sarcolemma of vascular smooth muscle, contribute to the causation of genetic and experimental hypertension, as well as to some changes in hypertension associated with volume expansion. Analysis of these causative factors may aid in treatment and, ultimately, allow the prevention of hypertension.
 ...
PMID:Pathophysiology of genetic and experimental hypertension. 244 90

Arteries respond to long-term changes in flow rate by alterations in caliber that tend to restore wall shear stress to normal baseline levels. Changes in radius, pressure, or geometric configuration elicit changes in structure and composition of the media in keeping with the altered level and distribution of tensile stresses. Similar stabilizing adaptations occur in the presence of conditions that induce the formation of atherosclerotic plaques, but the ultimate effectiveness of these reactions is variable. Several recent experiments provide information on the possible effects of hyperlipidemia on the smooth muscle cell (SMC) response to normal or increased levels of mechanical stress: (a) Normolipemic serum increases collagen synthesis by SMCs grown on purified elastin membranes compared to synthesis in serum-free medium, but synthesis is not further enhanced by cyclic stretching of the cells. Collagen production increase is less marked in hyperlipemic serum, but cyclic stretching raises synthesis to a degree comparable to that noted for serum-free medium. (b) The increase in artery diameter in response to increased flow rate and the elaboration of media components in relation to the increase in diameter are not hampered by hyperlipidemia. (c) The compensatory enlargement of arteries in response to plaque formation is not prevented by hyperlipidemia even in the presence of hypertension. (d) The healing of a transmural necrotizing injury of the media is, however, retarded and incomplete in the presence of hyperlipidemia. These findings indicate that hyperlipidemia per se does not necessarily interfere with the SMC response to mechanical stimuli. The usual adaptive reactions remain intact.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Limited effects of hyperlipidemia on the arterial smooth muscle response to mechanical stress. 247 33

The effects of renovascular hypertension and of its treatment with perindopril, a converting enzyme inhibitor, on the structure and function of large arteries were studied on 2 kidneys, 1 clip Goldblatt rats. One month after surgery, the animals rendered hypertensive (n = 24) and those who had had a blank operation (n = 24) were divided into two groups receiving either perindopril 1 mg/kg/day or distilled water during 4 week At the end of treatment haemodynamic values, including arterial pressure and instant blood flow at Doppler velocimetry, were measured in anaesthesized rats. The mechanical properties of the carotid artery were studied by in situ measurement of carotid compliance in response to imposed pressures. Finally, morphometric parameters of the thoracic aorta, including thickness of the media, density of elastin, collagen and nuclei and nuclear surface area, were studied by means of an automatized image analysis system. Hypertension was associated with a characteristic increase in aortic impedance (14,479 +/- 5,171 vs 9,022 +/- 4,071 dyn.sec/cm5; p less than 0.01) and a decrease in systemic arterial compliance (2.41 +/- 0.96 vs 3.92 +/- 1.15 x 10-3 ml/mmHg; p less than 0.05) and carotid compliance (6.31 +/- 1.85 vs 3.8 +/- 3.4 X 10-2 mm3/mmHg; p less than 0.05). Treatment with perindopril normalized the systolic and diastolic pressures and completely reversed the artery rigidity markers. Our morphometric analysis of the aortic wall enabled us to relate these functional changes to structural changes in vascular wall.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Effects of chronic inhibition of converting enzymes on the structure and function of the large arterial trunks in rats]. 250 10

Neonatal calves exposed to chronic hypobaric hypoxia develop severe pulmonary hypertension associated with altered vascular reactivity, cellular proliferation, and increased elastin and collagen production. We hypothesized that prostaglandin (PG) production would be decreased in the pulmonary arterial vessel wall of these calves. Further, because of the possibility that the hemodynamic stresses of hypoxic pulmonary hypertension might change along the longitudinal axis of the pulmonary circulation, we measured prostaglandin synthetic capability in tissues isolated from proximal pulmonary artery, distal pulmonary artery, and pulmonary vein. We found that PGI2 production was decreased in both proximal and distal pulmonary artery rings isolated from pulmonary hypertensive calves compared to controls. PGI2 production was greater in distal than in proximal lobar pulmonary artery. In contrast, pulmonary veins from hypertensive calves, which are protected from the hemodynamic stress of pulmonary arterial hypertension, did not demonstrate altered PGI2 production compared to controls. PGE2 production was also decreased in proximal hypertensive pulmonary arterial rings as compared to controls. To determine if this decrease in vessel wall production of prostaglandins was due to changes in cellular prostaglandin production, we studied prostaglandin production by the three major cell types comprising hypertensive and control arteries. Endothelial cells cultured from hypertensive main pulmonary artery produced less PGI2 than did those from control artery, and there appeared to be a shift from PGI2 production to PGE2 production in endothelial cells isolated from hypertensive artery. Explanted advential fibroblasts from hypertensive artery produced less PGE2 than did controls. Smooth muscle cell PGI2 production did not differ between cells isolated from hypertensive and control arteries in these brief 30-min incubations. We conclude that there is a relative deficit in PGI2 and PGE2 production in the pulmonary arteries of calves with hypoxia-induced pulmonary hypertension and speculate that this contributes to altered vascular tone and vessel remodeling.
 ...
PMID:Decreased arterial wall prostaglandin production in neonatal calves with severe chronic pulmonary hypertension. 251 77

The spontaneous rupture of the internal elastic lamina (IEL) in various arteries occurs to different extents in different rat strains. We have quantified this phenomenon in the caudal and renal arteries and abdominal aorta in two normotensive inbred strains: the Brown Norway (BN) and Long Evans (LE) strains. At 5 weeks of age, BN rats of both sexes exhibited small numbers of interruptions in the IEL of the caudal artery, whereas LE rats did not. Postpubertal male and female BN rats presented large numbers of IEL interruptions in the caudal artery and significant numbers in the renal artery and abdominal aorta, whereas LE rats showed few in the caudal artery and none in the other arteries. Treatment with beta-aminopropionitrile (BAPN, an inhibitor of lysyl oxidase, the enzyme involved in the formation of cross-links in elastin and collagen) increased the formation of IEL ruptures in both strains in the caudal and renal artery and in the abdominal aorta in BN rats, but not in the abdominal aorta of LE rats. Apart from IEL ruptures, which were more prevalent in BN rats, no differences were observed in the ultrastructure of the aortic elastic fibers between the two strains, either in controls or in BAPN-treated rats. When male rats of both strains were made hypertensive by unilateral nephrectomy and administration of deoxycorticosterone and salt, mortality was more precocious in the BN strain although blood pressure was significantly higher in the BN strain at only one time point. The incidence of cerebrovascular hemorrhage was 48% in BN rats and 0% in LE rats. Hypertension increased the formation of ruptures in the IEL in some arteries - to a greater extent in the BN than in the LE rats. These results raise the possibility that the propensity to spontaneous rupture of the IEL, which is in part genetically determined, may reflect a latent form of vascular fragility which becomes significant in hypertension, resulting in poor survival and susceptibility to cerebrovascular accidents.
 ...
PMID:Spontaneous rupture of the internal elastic lamina in the rat: the manifestation of a genetically determined factor which may be linked to vascular fragility. 257 18

The effects of renovascular hypertension and its treatment by a converting enzyme inhibitor (perindopril) on the structure and function of large arteries were studied in the Goldblatt 1 clip--2 kidney rat. One month after the surgical operation, the hypertensive animals (n = 24) and the sham operated animals (n = 24) were divided into two groups receiving either 1 mg/kg per day of perindopril or distilled water for four weeks. At the end of treatment, the hemodynamic parameters, including blood pressure and instantaneous blood flow measured by Doppler, were measured in anesthetized rats. The mechanical properties of the carotid artery were studied by in situ measurement of the carotid compliance in response to imposed pressures. Lastly, morphometric parameters of the thoracic aorta, including the thickness of the media, the density of elastin, collagen and nuclei and the area of the nuclei were studied by an automated image analysis system. Hypertension was associated with an increase in the characteristic impedance of the aorta (14,479 +/- 5,171 vs 9,022 +/- 4,071 dyne.sec/cm5; p less than 0.01) and a reduction in systemic arterial compliance (2.41 +/- 0.96 vs 3.92 +/- 1.15 x 10(-3) ml/mmHg; p less than 0.01) or carotid arterial compliance (6.31 +/- 1.85 vs 8.38 +/- 3.14 x 10(-2) mm3/mmHg; p less than 0.05). Treatment with perindopril normalized systolic and diastolic blood pressure and completely inverted the markers of rigidity of the large arteries. Morphometric analysis of the aortic wall allowed these functional modifications to be attributed to structural modifications of the wall. The thickness of the media was increased by hypertension (122.3 +/- 3.7 vs 97.5 +/- 4.4 microns; p less than 0.01). This thickening was attributed to hypertrophy of the smooth muscle cells as evidenced by the increase in the nucleus size (8.58 +/- 1.54 vs 7.38 +/- 0.78 microns 2; p less than 0.01). It was accompanied by an increase in the density of collagen (8.6 +/- 3.6 vs 7.3 +/- 2.4%; p less than 0.01) and a decrease in the density of elastin (31.9 +/- 8.3 vs 38.6 +/- 12.8%; p less than 0.01). Treatment with perindopril normalized the thickness of the media (103.0 +/- 4.8 microns) by reducing cellular hypertrophy. The short duration of treatment did not allow regression of the modifications in the density of the proteins of the interstitial matrix. In conclusion, renovascular hypertension severely alters the functional and structural properties of large arteries. Treatment with perindopril normalizes the properties of the vessel wall.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effects of chronic converting enzyme inhibition on the structure and function of large arteries in the rat. 260 98

We adapted a highly sensitive and reproducible ELISA technique for the determination of anti-elastin peptide antibodies of IgG type AEAb-IgG) and IgM type AEAb-IgM) in human sera. The determination was performed in the sera of 265 normal and diseased persons. The pathologies studied included obliterative arteriosclerosis of the legs, ischemic heart disease, stroke, diabetes mellitus, type IIb and IV hyperlipoproteinemia and hypertension. No clearcut correlation could be found between AEAb and age. In contrast, in arteriosclerotic patients and especially in obliterative arteriosclerosis of the legs and ischemic heart disease, the concentration of AEAb-IgG was significantly increased. The AEAb-IgM showed no change in the studied diseases. Both types of AEAb were decreased in type IV hyperlipoproteinemia. Anti-elastin antibodies may be involved in the pathomechanisms of the above diseases and the determination of antibody concentrations may be of some help in obliterative arteriosclerotic diseases.
 ...
PMID:Determination of anti-elastin peptide antibodies in normal and arteriosclerotic human sera by ELISA. 264 31

A family is described in which nine members over two generations had an aortic dissecting aneurysm or aortic or arterial dilation at a young age. The family has been followed up since 1977 after the death of a second teenager from a kindred of 11. None of the patients had the Marfan syndrome or a history of systemic hypertension. Three members died of ruptured aortic dissecting aneurysm and acute hemopericardium at 14, 18 and 24 years of age, respectively; a fourth member died suddenly at age 48 years, a few years after aortic repair for aneurysmal dilation. One member underwent surgical repair of an ascending aortic dissecting aneurysm at age 18 years and is still alive. Four members are currently under close medical observation for aortic or arterial dilation. Histologic examination of the aortic wall at autopsy or surgery in three patients revealed a loss of elastic fibers, deposition of mucopolysaccharide-like material in the media and cystic medial changes. Types I and III collagen from cultured fibroblasts appeared normal on gel electrophoresis. Results of indirect immunofluorescent studies of the elastin-associated microfibrillar fiber array in skin and fibroblast culture from multiple family members were also normal. This dramatic familial cluster of aortic dissecting aneurysm and aortic or arterial dilation suggests a genetically determined disease of autosomal dominant inheritance although the basic defect remains unknown.
 ...
PMID:Familial aortic dissecting aneurysm. 264 12

Insulin-like growth factor I stimulates mitogenesis in smooth muscle cells, and upregulates elastin synthesis in embryonic aortic tissue. Increased smooth muscle elastin synthesis may play an important role in vascular remodeling in chronic pulmonary hypertension. Therefore, we studied the effect of IGF-I on elastin and total protein synthesis by pulmonary arterial smooth muscle cells in vitro. Tropoelastin synthesis was measured by enzyme immunoassay, and total protein synthesis was measured by [3H]-leucine incorporation. In addition, the steady-state levels of tropoelastin mRNA were determined by slot blot hybridization. Incubation of confluent cultures with various concentrations of IGF-I resulted in a dose-dependent stimulation of elastin synthesis, with a 2.4-fold increase over control levels at 1000 ng/ml of IGF. The increase in elastin synthesis was reflected by a stimulation of the steady-state levels of tropoelastin mRNA. We conclude that IGF-I has potent elastogenic effects on vascular smooth muscle cells, and speculate that it may contribute to vascular wall remodeling in chronic hypertension.
 ...
PMID:Insulin-like growth factor I stimulates elastin synthesis by bovine pulmonary arterial smooth muscle cells. 265 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>