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

Left ventricular remodeling in hypertension is associated with cardiac interstitial and perivascular collagen deposition. The dual angiotensin I converting enzyme/neutral endopeptidase inhibitor omapatrilat (also called vasopeptidase inhibitor) improves left ventricular remodeling in experimental heart failure. We hypothesized that omapatrilat would induce regression of cardiac and vascular fibrosis in hypertension. We, therefore, investigated the effect of omapatrilat on collagen deposition in heart and aorta of stroke-prone spontaneously hypertensive rats (SHRSP). Twenty-week-old normotensive Wistar-Kyoto (WKY) rats, untreated SHRSP, and SHRSP treated with omapatrilat (40 mg/kg per day, orally) for 10 weeks were investigated. Collagen in the heart and the descending thoracic aorta was stained with Sirius red. After 10 weeks, systolic blood pressure (BP) was significantly (P < .01) reduced in omapatrilat-treated versus untreated SHRSP. Interstitial collagen density was significantly decreased in the subendocardial myocardium (to 2.71 +/- 0.24% v 4.12 +/- 0.30%, respectively, P < .05) and in the midmyocardium of omapatrilat-treated versus untreated SHRSP (to 3.01 +/- 0.25 v 4.19 +/- 0.17% respectively, P < .05). Perivascular collagen was significantly (P < .05) decreased in the subepicardial, mid-myocardial and, subendocardial regions of the myocardium of omapatrilat-treated versus untreated SHRSP. Aortic collagen content decreased in omapatrilat-treated versus untreated SHRSP (to 36.1 +/- 2.8 v 58.8 +/- 6.1 x 10(3) microm2/mm section, respectively, P < .05). In conclusion, in addition to being a potent antihypertensive agent, omapatrilat significantly improves cardiac and vascular fibrosis in SHRSP.
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PMID:Effect of ACE/NEP inhibition on cardiac and vascular collagen in stroke-prone spontaneously hypertensive rats. 1171 Jul 87

We investigated the effect of long-term in vivo blockade of the ET-1 receptor subtype B (ET(B)) with A-192621, a selective ET(B) antagonist, on atrial and ventricular natriuretic peptide (NP) gene expression in deoxycorticosterone acetate (DOCA)-salt hypertension. In this model, stimulation of the cardiac natriuretic peptide (NP) and the endothelin system and suppression of the renin-angiotensin system is observed. DOCA-salt induced significant hypertension, cardiac hypertrophy and increased NP plasma and left atrial and right and left ventricular NP gene expression. ET(B) blockade per se produced hypertension and left ventricular hypertrophy but induced little change on the levels of ventricular NP and only increased left atrial natriuretic factor (ANF) mRNA levels. Combined ET(B) blockade/DOCA-salt treatment worsened hypertension, increased left ventricular hypertrophy and induced right ventricular hypertrophy. All animals so treated had increased ventricular NP gene expression. Collagen III and beta-myosin heavy chain gene expression were enhanced in both the right and the left ventricle of DOCA-salt hypertensive rats. The results of this study suggest that the ET(B) receptor does not participate directly in the modulation of atrial or ventricular NP gene expression and that this receptor mediates a protective cardiovascular function. ET(B) blockade can induce significant ventricular hypertrophy without an increase in ANF or brain NP gene expression.
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PMID:Natriuretic peptide gene expression in DOCA-salt hypertension after blockade of type B endothelin receptor. 1183 12

Collagen vascular diseases commonly affect the heart; cardiovascular events are the major cause of mortality in people with these diseases. A striking feature of the cardiac involvement in individuals with systemic lupus erythematosus (SLE) and rheumatoid arthritis is aggressive and accelerated atherosclerosis; women with SLE in the 35- to 44-year-old age group are more than 50 times more likely to suffer myocardial infarction than are matched controls. Traditional risk factors contribute to the accelerated atherosclerosis, but cannot explain the extent of risk. It is possible that the inflammatory process, which is similar to the inflammatory process in atherosclerosis, pays a critical pathophysiologic role. It is critically important to identify the presence of traditional cardiovascular risk factors (eg, tobacco usage, hypertension, hypercholesterolemia, diabetes, homocysteinemia), and to modify these to secondary prevention targets. Cardiac valvular disease is common in individuals with SLE and rheumatoid arthritis; its presence should be anticipated and subacute bacterial endocarditis prophylaxis precautions initiated. Cardiac autonomic neuropathy and conduction disturbances are common in people with heart disease related to systemic sclerosis and human leukocyte antigen B27; these patients should be monitored carefully for evidence of dysrhythmias.
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PMID:Cardiovascular Complications of Collagen Vascular Disease. 1185 77

Recent genetic studies indicate that Alport syndrome and thin glomerular basement membrane disease (TMD) may both be due to COL4A3, COL4A4, and COL4A5 mutations, but there is continuing uncertainty concerning the diagnosis and management of patients without classic family history and symptoms. We examined kidney pathology and collagen alpha 3 to alpha 5(IV) expression in a series of 16 patients who presented with overlapping signs between TMD and Alport nephritis. All patients presented with hematuria, and 11 also had proteinuria, of whom 5 had nephrotic range proteinuria. Only 9 had family history of hematuria. In 9 of 16 (60%) we found premature glomerulosclerosis in the renal biopsies. Three of 16 had predominantly wide, lamellated glomerullar basement membranes (GBM), and in these, alpha 3 to alpha 5(IV) was absent in glomeruli or skin, diagnostic of Alport nephritis. One patient (12) had a very wide GBM with intramembranous lucencies but no lamellation. Skin biopsy was collagen alpha 5(IV) positive. Nine of 16 patients had predominantly thin GBM by electron microscopy, and 3 had thin and slightly lamellated GBM. Collagen alpha 3 to alpha 5(IV) expression in the kidney or skin biopsy was present in all of the latter 12 patients. Three patients had end-stage renal disease, 7 patients had hypertension, and 1 patient had chronic renal failure. We found that of the 16 patients with presumed TMD, 3 had X-linked Alport nephritis, 2 appeared to have autosomal recessive Alport nephritis, and the remaining patients had either an Alport or a TMD variant. The latter had histologic and/or clinical evidence of progressive renal disease, including premature glomerulosclerosis, hypertension, sustained proteinuria, and either thin or slight GBM lamellation focally, and preserved alpha 3 to alpha 5(IV) expression. These patients have a TMD variant, but an Alport variant with a potentially transmissible severe defect different from benign hematuria cannot be excluded.
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PMID:Histopathology, ultrastructure, and clinical phenotypes in thin glomerular basement membrane disease variants. 1220 17

Collagen types I and III (Col I and Col III) are the major fibrillar collagens produced by fibroblasts and myofibroblasts in the adult heart. Fibrillar collagen of the heart provides the structural scaffolding for cardiomyocytes and coronary vessels and imparts cardiac tissue with physical properties that include stiffness and resistance to deformation. In addition, fibrillar collagen may also act as a link between contractile element of adjacent cardiomyocytes and as a conduit of information that is necessary for cell function. As in other organs, collagen turnover of normal adult heart results from the equilibrium between the synthesis and degradation of Col I and Col III. A number of factors have been described that may alter the balance in favor of either the synthesis (e.g., angiotensin II-ANG II-) or the degradation. Predominance of synthesis over degradation leads to increased Col I and Col III deposition or fibrosis that accompanies cardiac diseases such as hypertensive heart disease. Fibrosis alters myocardial structure and function and adversely afects the clinical outcome of hypertensive patients. Various lines of evidence suggest that besides hypertension, systemically and/or locally produced ANG II may participate in the development of hypertensive myocardial fibrosis via activation of ANG II type 1 receptors (AT(1)R). The potential clinical relevance of this possibility is linked to the ability of antihypertensive drugs such as angiotensin converting enzyme inhibitors (ACEIs) and AT(1)R antagonists (ARAs) to reverse myocardial fibrosis beyond their antihypertensive efficacy.
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PMID:Regulation of myocardial fibrillar collagen by angiotensin II. A role in hypertensive heart disease? 1250 57

Collagenofibrotic glomerulopathy is considered as a form of glomerulopathy in which organized collagen type III progressively deposits. We report a case of this disease with widespread expression of collagen type V. A 65-year-old woman was admitted to our hospital for further evaluation of nephrotic-range proteinuria. The patient had had anemia and hypertension for 9 years, and proteinuria for 3 years. A renal biopsy specimen showed a remarkable mesangial expansion with Congo red-negative and periodic acid-Schiff-positive deposits. At the ultrastructural level, two forms of bundling fibers were found in the mesangium and subendothelial side of the glomerular basement membranes (GBM). The GBM itself appeared normal. Immunohistochemical investigation showed that the glomerular lesions were strongly reactive with both anti-collagen type-III and -V antibodies. Immunoelectron microscopy demonstrated collagen type V in both forms of bundling fibers. Despite therapy, her renal function declined. The clinical course and renal pathology of this case were in accordance with collagenofibrotic glomerulopathy except for the widespread expression of collagen type V. Collagen type V is a fibrillar collagen capable of forming banding fibrils. This report poses the question whether collagen type V accumulates only in this particular case or whether it is a normal component in collagenofibrotic glomerulopathy.
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PMID:Collagenofibrotic glomerulopathy with a widespread expression of type-V collagen. 1259 68

Acute and long-term (up to 56 days) evolution of geometry, structural properties, vascular smooth muscle (VSM) tone and histomorphometric properties of the rat common carotid arteries under induced hypertension were investigated. Hypertension was induced in 8-week old male Wistar rats by total ligation of the aorta between the two kidneys. Rats were sacrificed 2, 4, 8 and 56 days postsurgery. The arterial wall layers thicken non-uniformly during the adaptation process, the inner layers thicken more in the acute phase of hypertension, whereas the outer layers of the wall are thicker than the inner layers at the end of the adaptation phase. Collagen content in the wall media exhibits a non-linear evolution, with a rapid increase in the acute hypertension phase followed by a slower increase at long-term. The elastin content increase is slight and steady, whereas VSM shows a steady but considerable increase which outdoes the collagen increase in long-term phase. VSM tone increases rapidly in the acute phase of remodelling (0-8 days) and this increase in tone contributes to a considerable increase in arterial compliance in the operating pressure range. At long-term (56 days) VSM tone returns to near control level, but compliance is even further increased, which suggests that at long-term the compliance increase is attributed primarily to structural remodelling.
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PMID:Geometrical, functional, and histomorphometric adaptation of rat carotid artery in induced hypertension. 1269 97

In hypertension, aldosterone has been demonstrated to play a crucial role in cardiac fibrosis, which generally increases cardiac morbidity and death. However, few studies have reported the expression of the mineralocorticoid receptor (MR) and 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in the heart under hypertensive conditions. Therefore, in this study, spontaneously hypertensive rats (SHR) were examined to elucidate the possible actions of mineralocorticoids via binding to MR. Wister Kyoto Rat (WKY), SHR, stroke-prone SHR (SHRSP), and malignant SHRSP (M-SHRSP) were used. Total RNA was extracted from the left ventricle of these rats, and examined for the expression levels of MR, 11beta-HSD2 and Collagen types 1 and 3 using reverse transcription real-time quantitative polymerase chain reaction employing the Light Cycler Instrument. Blood pressure was significantly different among each group. The mean mRNA levels for MR, 11beta-HSD2 and Collagen types 1 and 3 in M-SHRSP were found to be significantly increased compared to those of WKY, whereas no significant differences in mRNA levels were detected among SHR and SHRSP. Findings from the present study appear to demonstrate that MR and 11beta-HSD2 mRNA significantly rise in the left ventricle of M-SHRSP and increase of these mRNA is one of the cause of cardiac fibrosis.
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PMID:The possible roles of mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 2 in cardiac fibrosis in the spontaneously hypertensive rat. 1294 33

Mechanical factors play a key role in activation of cardiac growth factor response in hemodynamic overload, and both cooperate in myocardial remodeling. The present study was performed to investigate whether a different growth factor response is activated in the right and left ventricles in aortocaval fistula and its effects on regional myocardial adaptation. Relations between regional growth factor expression (angiotensin II, insulin-like growth factor-I, and endothelin-1), myocyte shape changes, and collagen deposition were investigated at mRNA and peptide levels in adult pigs after the creation of an aortocaval fistula distal to the renal arteries (n=15) and in sham-operated animals (n=15). The role of angiotensin II was investigated by the administration of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist. In the left ventricle, pure volume overload was accompanied by persistent increase of insulin-like growth factor-I mRNA expression, peptide concentration (2.2-fold versus sham at 3 months, P<0.05), and significant increase of myocyte length (+29% at 3 months, P<0.05). Conversely, the mixed pressure-volume overload faced by the right ventricle resulted in significant regional overexpression of all growth factors investigated (angiotensin II, insulin-like growth factor-I, and endothelin-1), with corresponding increase of myocyte diameter and length and collagen deposition (+117% at 3 months). Collagen accumulation in the right ventricle as well as the increase in right ventricular end-diastolic pressure at the 3-month observation were inhibited by angiotensin II antagonism. The left and right ventricles respond differently to aortocaval fistula, and local growth factor expression is closely related to the regional myocardial adaptation.
Hypertension 2004 Jan
PMID:Different growth factor activation in the right and left ventricles in experimental volume overload. 1463 23

Remodeling of resistance arteries is a key feature in hypertension. We studied the transition of vasoconstriction to remodeling in isolated rat skeletal muscle arterioles. Arterioles activated with 10 nM endothelin-1 showed functional adaptation when kept at low distension in a wire myograph setup, where contractile properties shifted towards a smaller lumen diameter after 1 day. Pressurized arteries kept in organoid culture showed physical inward remodeling after 3-day activation with 10 nM endothelin-1, characterized by a reduction in relaxed diameter without a change in the wall cross-sectional area (eutrophic remodeling). The relaxed lumen diameter (at 60 mm Hg) decreased from 169 +/- 5 (day 0) to 155 +/- 4 microm (day 3). An antibody directed to the beta(3)-integrin subunit (but not one directed to the beta(1)-integrin subunit) enhanced remodeling, from a reduction in relaxed diameter at 60 mm Hg of 15 +/- 2.4 to 22 +/- 1.8 microm (both on day 3). Collagen gel contraction experiments showed that the antibody directed to the beta(3)-integrin subunit enhanced the compaction of collagen by smooth muscle cells, from 83 +/- 1.5 to 68 +/- 1.5% of the initial gel diameter. In conclusion, these data show that inward eutrophic remodeling is a response to sustained contraction, which may involve collagen reorganization through beta(3)-integrins.
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PMID:Activation of resistance arteries with endothelin-1: from vasoconstriction to functional adaptation and remodeling. 1501 11


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