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

These studies were undertaken to determine the relationship of early changes in the synthesis rates and contents of collagen, elastin, and soluble tissue protein of pulmonary arteries in rats exposed chronically to normobaric hyperoxia. The growth response of pulmonary arteries was characterized by proportionate increases in the contents of the three protein fractions after 7 days (130% of control) and 21 days (194% of control) of exposure. Fractional rates of protein synthesis were assessed both in vivo and in vitro with the use of several radiolabeled amino acids as tracers to minimize uncertainties of the relationships of the specific radioactivities of measured amino acid pools and the precursors for the proteins fractions. Values for fractional synthesis rates of collagen, elastin, and soluble protein in vitro in pulmonary arteries isolated from control rats were 2.2, 1.6, and 19%/day, respectively. Rates of synthesis of collagen and soluble protein in vitro were approximately 20% lower than that determined in control rats in vivo. The fractional synthesis rates of the three protein fractions in isolated arteries from experimental rats were unchanged after 1 day of hyperoxic exposure, decreased marginally after 3 days, and markedly increased after 7 days. At this time the absolute increments in the fractional synthesis rates of collagen (+4.7%/day) and elastin (+5.0%/day) were less than that of soluble tissue protein (+16%/day) and were more comparable to the accumulation rate of proteins in the tissue. The disproportionate increment in the fractional rate of soluble protein synthesis suggests that the fractional rate of degradation of soluble protein was also increased during the growth response in this model of hypertension.
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PMID:Protein synthesis in pulmonary arteries from rats exposed to hyperoxia. 843 Aug 19

The purpose of this study was to examine effects of hypertension on mechanics of cerebral arterioles in nongenetic and genetic models of chronic hypertension. Pressure (servo null) and diameter were measured in pial arterioles of anesthetized renal hypertensive rats (one-kidney, one clip), uninephrectomized normotensive rats, spontaneously hypertensive rats, and normotensive Wistar-Kyoto rats. During maximal dilatation with EDTA, external diameter of pial arterioles at 70 mm Hg pial arteriolar pressure was not significantly different in renal hypertensive and normotensive rats (86 +/- 5 [mean +/- SEM] versus 84 +/- 4 microns) but was less in spontaneously hypertensive rats than in Wistar-Kyoto rats (81 +/- 3 versus 92 +/- 3 microns; p < 0.05). Cross-sectional area of the arteriolar wall (histological) was greater in renal hypertensive than in normotensive rats (1,360 +/- 131 versus 952 +/- 89 microns 2; p < 0.05) and in spontaneously hypertensive rats than in Wistar-Kyoto rats (1,294 +/- 97 versus 817 +/- 86 microns 2; p < 0.05). The stress-strain relation obtained from pressure-diameter data during maximal dilatation with EDTA indicated that distensibility of pial arterioles, when fully relaxed, was greater in renal hypertensive and spontaneously hypertensive rats than in normotensive and Wistar-Kyoto rats. We used point-counting stereology to quantitate composition of pial arterioles in renal hypertensive rats. Cross-sectional area of smooth muscle and elastin was significantly greater in renal hypertensive than in normotensive rats (smooth muscle, 947 +/- 108 versus 620 +/- 62 microns 2; elastin, 101 +/- 11 versus 55 +/- 6 microns 2; p < 0.05), whereas cross-sectional area of collagen and basement membrane was not significantly different in the two groups (collagen, 6 +/- 1 versus 5 +/- 1 microns 2; basement membrane, 120 +/- 12 versus 104 +/- 8 microns 2). Thus, we conclude that 1) cerebral arterioles undergo hypertrophy in both renal hypertensive and spontaneously hypertensive rats; 2) cerebral arterioles in renal hypertensive rats do not undergo "remodeling" with a reduction in external diameter, whereas external diameter is smaller in spontaneously hypertensive than in Wistar-Kyoto rats; 3) distensibility of cerebral arterioles, when fully relaxed, is increased in renal hypertensive rats and is greater in spontaneously hypertensive than in Wistar-Kyoto rats; and 4) the distensible components of the arteriolar wall are increased disproportionately in cerebral arterioles of renal hypertensive rats, which may contribute to increases in arteriolar distensibility.
Hypertension 1993 Jun
PMID:Mechanics and composition of cerebral arterioles in renal and spontaneously hypertensive rats. 850 Aug 63

The goal of this study was to examine the hypothesis that increases in pulse pressure produce hypertrophy of cerebral arterioles, even in the absence of increases in mean pressure. Sprague-Dawley rats underwent creation of an arteriovenous fistula and clipping of one carotid artery at 1 month of age. Rats that underwent exposure of the abdominal aorta without fistula production and unilateral carotid clipping served as controls. At about 6 months of age, the mechanics of sham and clipped pial arterioles were examined in vivo in anesthetized rats. Stress-strain relations were calculated from measurements of pial arteriolar pressure (servo null) and diameter and cross-sectional area of the arteriolar wall. Point counting stereology was used to quantify individual components in the arteriolar wall. Before deactivation of smooth muscle with EDTA, cross-sectional areas of the vessel wall and pulse pressures in sham pial arterioles were significantly greater (P < .05) in arteriovenous fistula rats than in control rats (cross-sectional area, 1468 +/- 100 versus 1129 +/- 104 microns 2; pulse pressure, 26 +/- 1 versus 14 +/- 1 mm Hg). In contrast, systolic and mean pressures in sham arterioles were not significantly different and diastolic pressure was significantly less in arteriovenous fistula rats (systolic pressure, 69 +/- 1 versus 67 +/- 4 mm Hg; mean pressure, 52 +/- 2 versus 57 +/- 3 mm Hg; diastolic pressure, 43 +/- 2 versus 53 +/- 3 mm Hg). Carotid clipping normalized cross-sectional area of the vessel wall (1083 +/- 86 microns 2) and pulse pressure (12 +/- 1 mm Hg) in pial arterioles of arteriovenous fistula rats. During maximal dilatation, the stress-strain curve in sham arterioles of arteriovenous fistula rats was shifted to the right of the curve in control rats, which indicates that arteriovenous fistulae increase passive distensibility of cerebral arterioles. The proportion of distensible components in the vessel wall (smooth muscle, elastin, and endothelium) was increased in sham arterioles of arteriovenous fistula rats. These findings (1) suggest that increases in pulse pressure, even in the absence of increases in mean pressure, are sufficient to produce hypertrophy of cerebral arterioles and (2) provide support for the concept that increases in distensibility of cerebral arterioles in association with hypertrophy of the vessel wall may be related to alterations in wall composition.
Hypertension 1996 Feb
PMID:Effects of increased pulse pressure on cerebral arterioles. 856 36

Increased elastin production and accumulation is a rapid and sensitive response to elevated vascular wall stress in both systemic and pulmonary hypertension. While initially protecting the vessel wall, these structural changes may in the longer term result in reinforcement of the hypertensive state and contribute to the persistence of the pathology of hypertension. Rapid responses apparently uncorrelated with increased elastin mRNA, at least in the case of systemic vessels, suggest novel mechanisms perhaps including increased efficiency of message translation or matrix accumulation of the protein. Investigations using in vitro organ and cell culture models have indicated a role for phospholipases and protein kinases, including protein kinase C, in stretch-induced elastin synthesis. In addition, tyrosine phosphorylation of membrane/sub-membrane/cytoskeletal sensors, including focal adhesion kinase and members of the lipocortin family, have been shown to be important in this transduction mechanism. Because its turnover is normally very slow, additional vascular elastin accumulated during hypertensive episodes, together with its consequences for the physical properties of the vessel wall, may persist long after blood pressure is restored to normal levels. Thus, recent interest has been drawn to the possibility of achieving regression of accumulated matrix elastin by promoting turnover of this protein through activation of endogenous vascular elastase and collagenase activities.
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PMID:Elastin in systemic and pulmonary hypertension. 857 61

High blood pressure results in cardiac hypertrophy and fibrosis, increased thickness and stiffness of large artery walls, and decreased renal function. The objective of our study was to assess the role of endothelin, angiotensin II, and high blood pressure in the end-organ damage observed in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 10 weeks with either a mixed endothelin-A and endothelin-B receptor antagonist, bosentan (100 mg/kg per day), an angiotensin-converting enzyme inhibitor, enalapril (10 mg/kg per day), or a long-acting calcium antagonist, mibefradil (20 mg/kg per day). A group of SHR was left untreated, and a group of normotensive Wistar rats was used as control. At the end of treatment, maximal coronary blood flow was measured in isolated perfused hearts. Cardiac hypertrophy and fibrosis, aortic medial thickness, and extracellular matrix content were evaluated by quantitative morphometry. Proteinuria and urea and creatinine clearances were measured, and renal histopathology was assessed. SHR exhibited cardiac hypertrophy, perivascular fibrosis, and decreased maximal coronary blood flow. Aortic medial thickness was increased, whereas elastin density was decreased. Finally, SHR showed decreased urinary excretion and decreased urea and creatinine clearances. No renal histological lesions were observed. Although bosentan did not affect blood pressure, it normalized renal function and slightly decreased left ventricular hypertrophy and fibrosis. Enalapril and mibefradil were both effective in significantly decreasing blood pressure, left ventricular hypertrophy, and aortic medial thickness and improving coronary blood flow, but in contrast to bosentan, they did not improve creatinine clearance. We conclude that in SHR, high blood pressure plays a major role in end-organ damage and that endothelin may partly mediate renal dysfunction and cardiac remodeling independently of a direct hemodynamic effect.
Hypertension 1996 Sep
PMID:Endothelin antagonism in end-organ damage of spontaneously hypertensive rats. Comparison with angiotensin-converting enzyme inhibition and calcium antagonism. 879 20

Hypertension results in increased thickness and stiffness of large artery walls. The goal of our study was to assess the respective roles of humoral factors such as Ang II, endothelin and blood pressure in these aortic modifications. For this purpose, uninephrectomized rats received DOCA and high salt diet, and when hypertension was installed, they were treated for 5 weeks with either a long-acting calcium antagonist, mibefradil (30 mg/kg/day), an ACE inhibitor, enalapril (3 mg/kg/day), or a mixed ETA and ETB endothelin receptor antagonist, bosentan (100 mg/kg/day). A group of hypertensive rats was left untreated and a sham-operated group of normotensive rats was used for control. At the end of treatment, aortic medial thickness and elastin as well as collagen were evaluated by quantitative morphometry. DOCA-salt hypertensive rats exhibited a marked increase in medial thickness associated with no change in absolute content in extracellular matrix. Elastin relative density decreased in DOCA rats. Enalapril had no effect on arterial pressure. Bosentan decreased slightly (by 12 mm Hg), but not significantly, blood pressure. None of these drugs had an effect on medial thickness suggesting that in DOCA hypertensive rats neither Ang II nor endothelin play a significant role in the remodeling of the aorta. In contrast, mibefradil almost normalized arterial pressure, prevented medial hypertrophy and increased elastin density. Further studies are required in order to assess if this effect is directly linked to the blood pressure decrease or to another mechanism related to the calcium antagonistic property of mibefradil.
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PMID:Respective role of humoral factors and blood pressure in aortic remodeling of DOCA hypertensive rats. 923 40

The present study focuses on the differential response of three branch levels of the mesenteric resistance arterial vasculature of 450-gram Sprague-Dawley rats infused continuously with angiotensin II (A-II) for 4, 7 and 14 days at a rate of 435 ng/kg/min, with an associated period of hypertension. The three branch levels (types I, II and III) were characterized by light microscopy and immunostaining using monoclonal antibodies for proliferating cell nuclear antigen, ED-1 (specific for rat monocytes/macrophages) and alpha smooth muscle cell (SMC) actin. Cross-sectional areas of the vascular walls were determined morphometrically. In situ hybridizations were performed on paraffin sections using both sense and antisense 35S-labeled cRNA probes generated from rat SMC osteopontin and elastin cDNAs. In the type-I (penetrating) arteries from A-II-infused animals, there was massive fibrinoid necrosis, a marked fibroproliferative perivascular response, intense monocyte/macrophage infiltration, striking SMC osteopontin and elastin gene expression; SMC, fibroblast and monocyte/macrophage DNA synthesis; and significant increase in the cross-sectional areas of the vascular walls. In the same animals, DNA synthesis also occurred in the larger mesenteric arteries of types II and III where it is associated with significant enlargement of the walls by SMC hypertrophy but without overt morphologic damage. It is suggested that the monocyte/macrophage infiltration and fibroproliferative response of type-I arteries may be related to A-II-induced osteopontin gene expression. Angiotensin infusion in the rat may represent a reproducible model of microvascular injury that can be utilized to elucidate the cellular and molecular biology of a variety of disease states such as hypertension and diabetes mellitus.
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PMID:Immunohistochemical and molecular characterization of the differential response of the rat mesenteric microvasculature to angiotensin-II infusion. 892 18

This study was designed to characterize the hemodynamic and biochemical properties of the abdominal aorta in four genetically related inbred rat strains that express genetic hypertension and hyperactive behavior in varying combinations. These include (1) the spontaneously hypertensive rat (SHR), which is hypertensive, hyperactive, and hyperreactive to stress; (2) Wistar-Kyoto (WKY) rats, which express none of these traits; (3) WKHT rats, which are hypertensive but not hyperactive; and (4) WKHA rats, which are hyperactive and hyperreactive to stress, but normotensive. Together, these four strains allowed us to examine the structural and functional changes in the aorta in the hypertensive SHR, the most widely used animal model of genetic hypertension, while controlling for the variables of hyperactivity and hyperreactivity that are also expressed in the SHR. Four groups of animals of both sexes were studied: (1) WKY, n = 101, (2) WKHA, n = 33, (3) WKHT, n = 91, and (4) SHR, n = 28. Blood pressure (BP) was determined by tail plethysmography as well as direct intraarterial monitoring under anesthesia. Fixed specimens were prepared for histologic analysis and the wall thickness determined morphometrically. Quantification of soluble tissue protein, elastin, and collagen in the aortic tissue was determined by measuring leucine (leu), hydroxyproline (HP/leu), and desmosine (DES/leu). The hypertensive strains (SHR and WKHT) had significantly higher tail BP than the normotensive strains (WKY and WKHA)-WKY: 128.7 +/- 22.3; WKHA: 126.7 +/- 14.6; WKHT: 162.8 +/- 21.2; SHR: 164.2 +/- 36.1 (p < 0.0001). Additionally, intraaortic diastolic BP and mean BP were higher in SHR rats than in WKHT. Morphometric studies showed the media thickness in the SHR rats was significantly greater than in the WKY and WKHA rats and no different than in the WKHT rats. Significantly less of the aortic wall protein was present as elastin in the hypertensive rats (SHR and WKHT), as well as the hyperactive rats (WKHA), compared to rats that had neither trait (WKY). These studies provide new information regarding aortic structure and function in genetic hypertension using inbred strains to control for the hyperactivity/hyperreactivity traits that coexist with hypertension in the SHR. They reveal that hypertensive aortas have altered matrix proteins that cannot be explained simply on the basis of blood pressure alone.
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PMID:Hemodynamic and biochemical characteristics of the aorta in the WKY, SHR, WKHT, and WKHA rat strains. 895 87

Aortic dissection is not a popular disease but it should be listed in the disease to be excluded especially in acute emergent cases, because of its serious and protean clinical manifestations. While DeBakey classification was used over 30 years. Stanford classification is now widely accepted for its clinical availabilities. The features of the aortic dissection are 1) presence of the intimal tear at the proximal end in almost all cases, 2) its frequent location in the ascending aorta and aortic segment just distal to the left subclavian artery, and 3) the dissected plane at the outer media or medial-adventitial border. Systemic hypertension is frequently noticed in cases with aortic dissection. These features suggest hemodynamic effect as a pathogenic factor in addition to mural fragility of the aorta. Aortic dissection is frequently encountered in Marfan syndrome and other heritable diseases of connective tissue. Concerning Marfan syndrome, mutation of fibrillin gene was confirmed. Fibrillin is a microfibril consisting of glycoprotein closely bound to elastin. Therefore, traditional "cystic medial necrosis" which was referred as a principal morphological change corresponding to aortic dissection is now thought to be a secondary change to the aortic injuries occurred in the aortic wall.
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PMID:[Pathology of aortic dissection]. 896 88

Extracellular matrix (ECM) in the heart and vascular wall includes fibrous proteins and proteoglycans. Fibrous proteins are classified within two categories: structural (collagen and elastin) and adhesive molecules (laminin and fibronectin). These ECM components are important in maintenance of both structure and function of the heart and vascular tissues. Myocardial infarction, hypertrophy, hypertension and heart failure are well known to be associated with progressive cardiac fibrosis. Vascular hypertrophy and thickening has been associated with the pathological series of events that attends both hypertension and restenosis. The accumulation of ECM in the cardiovascular system plays an important role in the development of heart failure after myocardial infarction and hypertension, as well as in vascular hypertrophy and restenosis. Angiotensin II (angiotensin) and transforming growth factor beta 1 are known to play a role in signalling the abnormal accumulation of ECM in these cardiovascular diseases. Administration of angiotensin-converting enzyme inhibitor or angiotensin receptor type 1 antagonist is associated with regression of cardiac hypertrophy and fibrosis as well as vascular hypertrophy.
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PMID:Extracellular matrix and cardiovascular diseases. 898 66


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