UMLS:C0020538 - FACTA Search

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

Angiotensin II (Ang II) infusion in rats augments vascular injury in balloon-injured carotid arteries and induces marked vascular and tubulointerstitial injury in kidneys. We examined how the AT1 receptor is modulated and whether blockade of the receptor with losartan could prevent the phenotypic and cellular changes. We also examined the role of the local renin-angiotensin system (RAS) by examining the expression of angiotensin-converting enzyme (ACE) and the effect of treatment with the ACE inhibitor, ramipril. Ang II infusion resulted in systemic hypertension and accelerated intimal and medial thickening in balloon-injured carotid arteries. Renal injury was manifested by proteinuria, glomerular phenotypic changes (mesangial expression of alpha-actin and podocyte expression of desmin), and tubulointerstitial injury with the tubular upregulation of the macrophage-adhesive protein, osteopontin, the interstitial accumulation of macrophages and myofibroblasts, and the deposition of collagen types III and IV. Ang II infusion decreased AT1 receptor number in the renal interstitium but not in glomeruli. Losartan completely blocked the Ang II-mediated hypertension, proteinuria, and injury to both carotid and kidney. Ang II infusion was also associated with an increase in ACE protein in both the proximal tubular brush border as well as at interstitial sites of injury, but despite evidence for activation of the local RAS, treatment with ramipril was without effect. These studies demonstrate that the renal and vascular injury induced by Ang II infusion is mediated by the AT1 receptor despite downregulation of the receptor in the interstitium. In addition, although there is evidence for local RAS activation, the injury appears to be mediated solely by the exogenous Ang II.
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PMID:Renal and vascular injury induced by exogenous angiotensin II is AT1 receptor-dependent. 1117 28

Prolonged stimulation with adrenocorticotropic hormone (ACTH) causes hypertension and increases Na+ intake and urine output in humans and animals. However, its biochemical basis remains to be established. Since renal Na+/H+ exchanger isoforms (NHE) and the sodium pump play an important role in this condition, their levels were examined in rats stimulated with ACTH. Male Wistar rats received daily sc injection of ACTH (30 microg/100 g of body wt) for 4 d. Half of the ACTH-stressed rats were kept for four additional days without injection of ACTH (poststimulation). In a third group, the animals were treated with dexamethasone (50 microg/100 g of body wt) daily for 4 d. A fourth group consisted of unstressed control animals. Levels of NHE proteins were measured by Western blot analysis. Sodium pump activity was assessed by the level of ouabain-sensitive K-stimulated p-nitrophenylphosphatase activity (PNP) in the renal cortex. ACTH caused a selective decrease in NHE-3, but not of NHE-1 or alpha-actin levels. Interestingly, this ACTH-induced change was not duplicated in the animals treated with dexamethasone. Immunofluorescence data demonstrated that NHE-3 is located in the renal proximal tubules. PNP activity, on the contrary, was increased in both the ACTH-stimulated and dexamethasone-treated animals. More important, these changes in NHE-3 and PNP activity returned to the control level poststimulation. In conclusion, while PNP upregulation may be mediated by adrenocortical glucocorticoid, a role for glucocorticoids in the suppression of NHE-3 is less clear. These changes might impair renal tubular Na+ reabsorption and hence increase Na+ and water excretion in ACTH stimulation, thus acting as a counterbalance to normalize blood pressure in ACTH-stimulated animals.
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PMID:Selective suppression of renal Na+/H+ exchanger isoform-3 by prolonged stimulation of rats with adrenocorticotropic hormone. 1195 62

This study examined the role of transforming growth factor-beta (TGF-beta) in the development of hypertension and renal disease in 9-wk-old male Dahl salt-sensitive (Dahl S) rats fed an 8% NaCl diet for 3 wk. The rats received an intraperitoneal injection of a control or an anti-TGF-beta antibody (anti-TGF-beta Ab) every other day for 2 wk. Mean arterial pressure was significantly lower in Dahl S rats treated with anti-TGF-beta Ab (177 +/- 3 mmHg, n = 12) than in control rats (190 +/- 4 mmHg, n = 17). Anti-TGF-beta Ab therapy also reduced proteinuria from 226 +/- 20 to 154 +/- 16 mg/day. Renal blood flow, cortical blood flow, and creatinine clearance were not significantly different in control and treated rats; however, medullary blood flow was threefold higher in the treated rats than in the controls. Despite the reduction in proteinuria, the degree of glomerulosclerosis and renal hypertrophy was similar in control and anti-TGF-beta Ab-treated rats. Renal levels of TGF-beta1 and -beta2, alpha-actin, type III collagen, and fibronectin mRNA decreased in rats treated with anti-TGF-beta Ab. To examine whether an earlier intervention with anti-TGF-beta Ab would confer additional renoprotection, these studies were repeated in a group of 6-wk-old Dahl S rats. Anti-TGF-beta Ab therapy significantly reduced blood pressure, proteinuria, and the degree of glomerulosclerosis and renal medullary fibrosis in this group of rats. The results indicate that anti-TGF-beta Ab therapy reduces blood pressure, proteinuria, and the renal injury associated with hypertension.
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PMID:Antihypertensive effects of chronic anti-TGF-beta antibody therapy in Dahl S rats. 1218 11

The effects of risk modifiers such as diabetes, obesity and hypertension on vascular healing after stent deployment are largely unknown, because of a lack of an appropriate animal model to study. Since many inbred strains of rats expressing these phenotypes are available, we validated a carotid artery model of in-stent restenosis in the rat. A detailed histomorphometric analysis was performed on 2-cell Multi-Link(TM) stents (1.5 x 5 mm) deployed in the common carotid artery of male Wistar rats. Early focal thrombus formation around stent struts with adherent leukocytes was evident by day 3. The number of ED-1-positive macrophages was maximal by day 7 and declined markedly thereafter. Neointimal cell proliferation peaked by day 7 (19.3 +/- 6.9) and progressively decreased to <2% by day 60. By day 14, neointimal area was significantly increased (0.39 +/- 0.03 vs. 0.18 +/- 0.05 mm(2) at day 7, p = 0.003) characterized by an enhanced number of alpha-actin-positive smooth muscle cells surrounded by extracellular matrix rich in versican and hyaluronan. At day 28, neointimal area was maximal accompanied by an appreciable decrease in the staining intensity for hyaluronan and versican. By day 60, neointimal area decreased significantly (0.28 +/- 0.04 vs. 0.45 +/- 0.07 mm(2) at day 28, p = 0.04) independent of a change in cell density. This regression phase was accompanied by a marked increase in elastin fibrils and collagen type I. In summary, vascular healing following carotid artery stenting in the rat parallels that of larger animals; however, it is accelerated relative to humans.
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PMID:A novel rat model of carotid artery stenting for the understanding of restenosis in metabolic diseases. 1229 4

In a recent study we described an increase of elastic tissue fibres in blood vessel walls of placental stem villi during pre-eclampsia when compared to uncomplicated pregnancies. Furthermore, the thickness of these blood vessel walls was enhanced in pre-eclampsia. Since it is known that elastic tissue fibres increase in systemic hypertension, it may be assumed that the enhancement of elastic tissue fibres in placental stem villi during pre-eclampsia may be induced by the hypertension. To get further insight into this assumption, we examined the amount of elastic tissue fibres in stem villus blood vessels of placentae of pregnancies complicated by intrauterine growth retardation (isolated IUGR, fourteen cases), a disease without hypertension of the mother and such with pre-eclampsia and concomitant IUGR (IUGR+PE, nine cases). Each study group was compared with uncomplicated pregnancies (twenty-six cases). Unfixed cryostat serial sections were processed for conventional orcein staining and for the demonstration of alpha-actin-immunoreactivity. The intensity of orcein staining of stem villus blood vessel walls was evaluated by a semiquantitative score method. Significant lower intensities of orcein staining were calculated for blood vessel walls of placentae of isolated IUGR (P=0.0007) and IUGR+PE (P=0.0039) when compared to uncomplicated pregnancies each. Additionally, the blood vessel wall thickness of stem villi of isolated IUGR (P=0.0081) and IUGR+PE (P=0.0007) was significantly reduced. In comparison to the above mentioned investigation, our results show that, in contrast to isolated pre-eclampsia, elastic tissue fibres are decreased during pregnancies complicated by IUGR, independently of the occurrence of concomitant pre-eclampsia when compared to uncomplicated pregnancies. From our studies it may be considered that the increase of elastic tissue fibres in placentae of patients with isolated pre-eclampsia may be induced by systemic hypertension. Furthermore, our study underline arguments that IUGR may be an independent disease of the fetus.
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PMID:Decrease of elastic tissue fibres in stem villus blood vessels of the human placenta during IUGR and IUGR with concomitant pre-eclampsia. 1238 42

Garlic causes reduction in blood pressure (BP), however the role of Na/H exchanger (NHE) which mediates hypertension and related tissue-damage is poorly understood. In this study the effect of an established dose of raw garlic extract was investigated on the expression of NHE-1 and -3 and sodium pump activity in a 2K-1C model of hypertension in rats. 2K-1C animals showed high BP, increased serum concentration of PGE2 and TxB2, hypertrophy of the unclipped kidneys, but not in the clipped kidneys In addition, NHE-1 and NHE-3 isoforms were increased in both the 2K-1C kidneys, whereas alpha-actin was increased in the clipped but not in unclipped kidneys. Sodium pump activity was decreased in the clipped kidneys, but remained unchanged in the unclipped kidneys. Garlic treatment reduced the induction of NHE-1 only in the unclipped 2K-1C kidneys, whereas garlic treatment increased the sodium pump activity in both the 2K-1C kidneys. These findings demonstrate that the antihypertensive action of garlic is associated with a reversal of NHE-1 induction in the unclipped kidneys. Induction of NHE isoforms together with a reduced sodium pump activity might cause necrosis in the 2K-1C clipped kidneys due to cellular retention of Na+. On the other hand, activation of sodium pump by garlic extract in the kidneys should reduce intracellular Na+ concentration and normalize BP. These findings signify the use of garlic in the treatment of hypertension.
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PMID:Mechanism of garlic (Allium sativum) induced reduction of hypertension in 2K-1C rats: a possible mediation of Na/H exchanger isoform-1. 1290 30

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease, which may afflict as many as 1 in 500 subjects (0.2%), being probably the most common hereditary cardiovascular disease and the most common cause of sudden cardiac death (SCD). Hypertrophic cardiomyopathy is characterized by the presence of unexplained left ventricular hypertrophy (in absence of hypertension, valvular disease, etc), which is usually asymmetric and involves the ventricular septum. Molecular genetic studies have identified eleven genes that code proteins of the sarcomere that are associated with the HCM; the beta-myosin heavy chain gene (MYH7), alpha-myosin heavy chain (MYH6), cardiac troponin T (TNNT2); cardiac troponin C (TNNC1), alpha-tropomyosin (TPM1), myosin binding protein-C (MYBPC3), cardiac troponin (TNNI3), essential and regulatory light chain genes (MYL3 and MYL2, respectively), cardiac alpha-actin gene (ACTC) and titin (TTN). The objective of this paper is the revision of the current state of the knowledge on (1) the organization and mutations of the HCM causing genes and their proteins and (2) the animal models developed for the study of the genes, mutations and proteins in the hypertrophic cardiomyopathy.
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PMID:[Familial hypertrophic cardiomyopathy: genes, mutations and animal models. A review]. 1505 60

Hypertension and anemia may be causes of left ventricular hypertrophy (LVH) in uremia but the molecular mechanism is not known. Uremia was induced in male Spraugue Dawley rats by 5/6 nephrectomy. The following groups of rats were studied for 6 weeks; uremic rats (U) fed ad. lib., control rats (C) pair-fed with U, U rats given hydralazine (100 mg/kg/day) (UH), U rats given erythropoietin (48 U/kg/week, i.p.) (UE). Both diastolic and mean arterial pressures are higher (P < 0.01) in U and UE compared with C whereas both pressures in UH were normalized. Hemoglobin in U was lower than in C, and was normalized in UE. U, UH and UE had higher heart weight/body weight ratios (HW/BW) as well as left ventricular weight/body weight ratios (LV/BW) compared with C (P < 0.01). Compared with U, UH has lower HW/BW and LV/BW (P < 0.05) and UE has normal HW/BW but lower LV/BW than U (P < 0.05). To see if the gene expression in uremic LVH is similar to that described in pressure overload LVH in which mRNA levels of angiotensin converting enzyme (ACE), transforming growth factor-beta1 (TGF-beta1), atrial natriuretic factors (ANF) and skeletal a- actin were increased, we measured these mRNA levels by Northern analysis. TGF-beta1, ACE and alpha-actin mRNA levels were not changed in all 4 groups. ANF mRNA in U and UE was increased 3 fold over C, and normalized in UH. Treatment of anemia with erythropoietin improved uremic LVH but did not change ANF mRNA; whereas treatment of hypertension with hydralazine normalized ANF mRNA but did not completely correct uremic LVH. Thus, gene expression in uremic LVH is distinct from that in pressure-overload LVH, suggesting that other unidentified factor(s) might be involved in uremic LVH.
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PMID:Gene expression in uremic left ventricular hypertrophy: effects of hypertension and anemia. 1527 37

Ephedra, a herb reported to suppress appetite and stimulate the sympathetic nervous system as well as cardiac performance, has recently been related to several adverse events, including seizure, stroke, hypertension, myocardial infarction, and sudden death. Here, we describe the case of a 45-year-old woman who died of cardiovascular collapse while taking ephedra. Tissue analysis revealed non-specific degenerative alterations in the myocardium (lipofuscin accumulation, basophilic degeneration and vacuolation of myocytes, as well as myofibrillary loss), associated with myocyte apoptosis, caspase activation, and extensive cleavage of miofibrillary proteins alpha-actin, alpha-actinin, and cardiac troponin T. Healthcare professionals are therefore urged to warn their patients about the risk of serious adverse effects, which may follow ephedra intake.
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PMID:A case of fatal ephedra intake associated with lipofuscin accumulation, caspase activation and cleavage of myofibrillary proteins. 1605 66

Vascular calcification is often encountered in advanced atherosclerotic lesions and is a common consequence of aging. Calcification of the coronary arteries has been positively correlated with coronary atherosclerotic plaque burden, increased risk of myocardial infarction, and plaque instability. Chronic kidney disease (CKD) patients have two to five times more coronary artery calcification than healthy age-matched individuals. Vascular calcification is a strong prognostic marker of cardiovascular disease mortality in CKD patients. Vascular calcification has long been considered to be a passive, degenerative, and end-stage process of atherosclerosis and inflammation. However, recent evidence indicates that bone matrix proteins such as osteopontin, matrix Gla protein (MGP), and osteocalcin are expressed in calcified atherosclerotic lesions, and that calcium-regulating hormones such as vitamin D3 and parathyroid hormone-related protein regulate vascular calcification in in vitro vascular calcification models based on cultured aortic smooth muscle cells. These findings suggest that vascular calcification is an actively regulated process similar to osteogenesis, and that bone-associated proteins may be involved in the development of vascular calcification. The pathogenesis of vascular calcification in CKD is not well understood and is almost multifactorial. In CKD patients, several studies have found associations of both traditional risk factors, such as hypertension, hyperlipidemia, and diabetes, and uremic-specific risk factors with vascular calcification. Most patients with progressive CKD develop hyperphosphatemia. An elevated phosphate level is an important risk factor for the development of calcification and cardiovascular mortality in CKD patients. Thus, it is hypothesized that an important regulator of vascular calcification is the level of inorganic phosphate. In order to test this hypothesis, we characterized the response of human smooth muscle cell (HSMC) cultures to inorganic phosphate levels. Our findings indicate that inorganic phosphate directly regulates HSMC calcification through a sodium-dependent phosphate transporter mechanism. After treatment with elevated phosphate, there is a loss of smooth muscle lineage markers, such as alpha-actin and SM-22alpha, and a simultaneous gain of osteogenic markers such as cbfa-1 and osteocalcin. Elevated phosphate may directly stimulate HSMC to undergo phenotypic changes that predispose to calcification, and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. Furthermore, putative calcification inhibitory molecules have been identified using mouse mutational analyses, including MGP, beta-glucosidase, fetuin-A, and osteoprotegerin. Mutant mice deficient in these molecules present with enhanced cardiovascular calcification, demonstrating that specific molecules are normally important in suppressing vascular calcification. These findings suggest that the balance of inducers, such as phosphate, and inhibitors, such as MGP, fetuin-A, and others, are likely to control whether or not calcification occurs under pathological conditions.
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PMID:Vascular calcification in chronic kidney disease. 1650 29

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