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)

The abnormal proliferation of cardiac fibroblasts is involved in the pathophysiologic process of left ventricular hypertrophy (LHV) associated with essential hypertension. Arginine vasopressin (AVP) has been reported to contribute significantly to the pathogenesis of hypertension. In this study, the authors investigated the effects of AVP and its V1 receptor antagonist [d(CH2)5Tyr2(Me)]AVP on the growth of rat cardiac fibroblasts. Cardiac fibroblasts of neonatal Sprague-Dawley rats were isolated, and growth-arrested cardiac fibroblasts were stimulated with 2.5% fetal calf serum in the presence and absence of AVP (0.001, 0.01, 0.1, and 1 microM) and [d(CH2)5Tyr2(Me)]AVP (0.1 microM). DNA synthesis was measured by [3H]thymidine incorporation. Thiazolyl blue assay and flow cytometry techniques were adopted to measure cell numbers and analyze cell cycle, respectively. Arginine vasopressin (0.1 and 1 microM) significantly increased DNA synthesis in cardiac fibroblasts. Moreover, AVP (0.1 and 1 microM) significantly increased the number of cardiac fibroblasts. Analysis of cell cycle showed that AVP (0.1 microM) increased S-stage percentage and proliferation index (PI). The V1 receptor antagonist [d(CH2)5Tyr2(Me)]AVP (0.1 microM) significantly inhibited DNA synthesis in cardiac fibroblasts. The cell number, S-stage percentage, and PI induced by AVP (0.1 microM) were significantly decreased by [d(CH2)5Tyr2(Me)]AVP (0.1 microM). These findings suggest that AVP might promote the proliferation of rat cardiac fibroblasts, which seems to be mediated via the V1 receptor. Arginine vasopressin may be involved in the pathophysiologic process of LVH by promoting cardiac fibroblast proliferation.
 ...
PMID:Effects of arginine vasopressin on growth of rat cardiac fibroblasts: role of V1 receptor. 1282 38

Recent studies have demonstrated the tissue-specific effect of Na+/K+ pump inhibition by ouabain and other cardiac glycosides on cell viability. The vascular endothelium is an initial target of cardiac glycosides employed for the management of congestive heart failure as well as circulating endogenous ouabain-like substances (EOLS), the production of which is augmented in volume-expanded hypertension. This study examined the role of the Na+/K+ pump in the survival of cultured porcine aortic endothelial cells (PAEC). Complete Na+/K+ pump inhibition with ouabain led to PAEC death, indicated by cell detachment and decreased staining with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Based on cell swelling and resistance to benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD.fmk) a pan-caspase inhibitor, this type of cell death was classified as necrosis. In contrast to ouabain, Na+/K+ pump inhibition in K+-free medium did not affect PAEC viability and sharply attenuated apoptosis triggered by 3H decay-induced DNA damage. Necrosis evoked by ouabain was preserved after dissipation of the transmembrane gradient of K+ and Na+, whereas dissipation of the Na+ gradient abolished the antiapoptotic action of K+-free medium. Comparative analysis of these results and modulation of intracellular Na+ and K+ content by the above-listed stimuli showed that interaction of ouabain with Na+/K+-ATPase triggered necrosis independently of inhibition of Na+/K+ pump-mediated ion fluxes and inversion of the [Na+]i/[K+]i ratio, whereas protection against apoptosis under Na+/K+ pump inhibition in K+-depleted medium was mediated by [Na+]i elevation. The role of Na+/K+ pump-mediated regulation of endothelial cell survival and vascular remodelling seen in hypertension should be investigated further in context of EOLS and chronic treatment with digitalis.
 ...
PMID:Na+/K+ pump and endothelial cell survival: [Na+]i/[K+]i-independent necrosis triggered by ouabain, and protection against apoptosis mediated by elevation of [Na+]i. 1506 61

Crocin, the digentiobiosyl ester of crocetin, was investigated for its cytoprotective effect on hydrogen peroxide-induced injury in bovine aortic endothelial cells (BAECs). The morphology of BAECs was observed by inverted phase contrast and electron microscopy. The MTT assay was used to measure cell viability. Cell apoptosis was evaluated by DNA argarose gel electrophoresis. The cells treated with H(2)O(2) (200 microM) showed apoptotic changes as revealed by cell shrinkage, condensation of nuclei, membrane blebbing and formation of apoptotic body. A concentration-dependent inhibition of cell injury was seen in cultures treated with crocin at dosages ranging from 1 to 10 microM. Furthermore, in the H(2)O(2)-treated group, agarose gel electrophoresis displayed a "DNA ladder". Whereas in the 10 microM crocin-pretreated group, cells remained intact and no "DNA ladder" was observed in agarose gel electrophoresis. Only very little DNA debris appeared on DNA-fragmentation analysis in the 1 muM crocin-pretreated group. Our data demonstrated that crocin has preventive effects on the cell apoptosis induced by H(2)O(2), which may contribute to its utilisation for cardiovascular diseases (e.g., atherosclerosis and hypertension).
 ...
PMID:Evidence of crocin against endothelial injury induced by hydrogen peroxide in vitro. 1675 86

1. We have isolated a novel human erythrocyte-derived depressing factor (EDDF) that has a significant antihypertensive effect in various rat models of hypertension. The aim of the present study was to examine the mechanisms of action of EDDF on vascular function in two-kidney, one-clip (2K1C) renovascular hypertensive rats. 2. The EDDF was prepared from human erythrocytes. Experiments were performed in 18 male Wistar rats. The vascular ring perfusion assay and a two-photon laser scanning fluorescence microscope (TMP) were used to evaluate the vascular contractile response. The effects of EDDF on phenylephrine (PE)- and noradrenaline (NA)-induced vascular contraction were evaluated in 2K1C hypertensive rats. The proliferation and DNA synthesis in vascular smooth muscle cells (VSMC) were determined using the [3H]-TdR (thymidine) incorporation and 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Flow cytometry, reverse transcription-polymerase chain reaction and western blots were used to measure cell cycle and apoptotic profiles, platelet-derived growth factor (PDGF)-A expression and the activity of extracellular signal-regulated kinase (ERK)-1/2, as well as the expression of cyclin D1 and cyclin-dependent kinase (CDK) 4. 3. At 10(-5) g/mL, EDDF significantly decreased the PE- and NA-induced hypertensive vascular contraction. In addition, EDDF inhibited DNA synthesis in primary VSMC from 2K1C rats. The mRNA expression of PDGF-A in VSMC was twofold higher in 2K1C rats compared with control rats, whereas EDDF significantly inhibited the increment in PDGF-A mRNA expression. In addition, EDDF inhibited the phosphorylation of ERK1/2 and decreased the expression of cyclin D1 and CDK4; p21 (Cip1) levels were increased after treatment with EDDF. 4. In conclusion, EDDF inhibits VSMC proliferation in 2K1C rats through G0/G1 cell cycle arrest. The effects may be mediated, in part, by enhanced expression of p21 (Cip1) and the inhibition of ERK1/2 phosphorylation and the expression of cyclin D1/CDK4 and PDGF-A.
 ...
PMID:Protective role of a novel erythrocyte-derived depressing factor on blood vessels of renovascular hypertensive rats. 1743 6

It has been suggested that an endogenous inhibitor of the sodium pump, identified as ouabain, contributes to the regulation of blood pressure and the pathogenesis of certain forms of hypertension. Vascular endothelial cells, whose functional integrity is crucial for the maintenance of blood flow and the antithrombotic activity, could be a target for endogenous ouabain. We studied the effect of ouabain on human umbilical vein endothelial cells (HUVEC) and found that nanomolar concentrations of the glycoside have an antiapoptotic activity that is dependent on the activation of phosphatidylinositol 3 kinase (PI-3K) and extracellular signal-regulated kinases (ERKs). At the same concentrations we found that ouabain affects the endocytosis of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) through the activation of signaling proteins such as Src kinase. This review sumarizes our findings on the effect of ouabain on HUVEC, the signal transduction pathways involved and the significance of these observations on the pathophysiology of endothelial function.
 ...
PMID:Vascular endothelium as a target for endogenous ouabain: studies on the effect of ouabain on human endothelial cells. 1753 38

The sympathetic nervous system plays an important role in the regulation of blood pressure. There is increasing evidence for positive and negative interactions between dopamine and adrenergic receptors; the activation of the alpha-adrenergic receptor induces vasoconstriction, whereas the activation of dopamine receptor induces vasorelaxation. We hypothesize that the D1-like receptor and/or D3 receptor also inhibit alpha1-adrenergic receptor-mediated proliferation in vascular smooth muscle cells (VSMCs). In this study, VSMC proliferation was determined by measuring [3H]thymidine incorporation, cell number, and uptake of 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT). Norepinephrine increased VSMC number and MTT uptake, as well as [3H]thymidine incorporation via the alpha1-adrenergic receptor in aortic VSMCs from Sprague-Dawley rats. The proliferative effects of norepinephrine were attenuated by the activation of D1-like receptors or D3 receptors, although a D1-like receptor agonist, fenoldopam, and a D3 receptor agonist, PD-128907, by themselves, at low concentrations, had no effect on VSMC proliferation. Simultaneous stimulation of both D1-like and D3 receptors had an additive inhibitory effect. The inhibitory effect of D3 receptor was via protein kinase A, whereas the D1-like receptor effect was via protein kinase C-zeta. The interaction between alpha1-adrenergic and dopamine receptors, especially D1-like and D3 receptors in VSMCs, could be involved in the pathogenesis of hypertension.
 ...
PMID:Inhibitory effect of D1-like and D3 dopamine receptors on norepinephrine-induced proliferation in vascular smooth muscle cells. 1844 Nov 98

AngiotensinII (AngII) induces vascular smooth muscle cell (VSMC) proliferation, which plays an important role in the development and progression of hypertension. AngII-induced cellular events have been implicated, in part, in the activation of protein kinase C (PKC) and extracellular signal-regulated kinases 1/2 (ERK1/2). In the present study, we investigated the effect of Ib, a novel nonpeptide AngII receptor type 1 (AT(1)) antagonist, on the activation of PKC and ERK1/2 in VSMC proliferation induced by AngII. MTT, and [(3)H]thymidine incorporation assay showed that AngII-induced VSMC proliferation was inhibited significantly by Ib. The specific binding of [(125)I]AngII to AT(1) receptors was blocked by Ib in a concentration-dependent manner with IC(50) value of 0.96nM. PKC activity assay and Western blot analysis demonstrated that Ib significantly inhibited the activation of PKC and phosphorylation of ERK1/2 induced by AngII, respectively. Furthermore, AngII-induced ERK1/2 activation was obviously blocked by GF109203X, a PKC inhibitor. These findings suggest that the suppression of Ib on AngII-induced VSMC proliferation may be attributed to its inhibitory effect on PKC-dependent ERK1/2 pathway.
 ...
PMID:PKC-dependent extracellular signal-regulated kinase 1/2 pathway is involved in the inhibition of Ib on AngiotensinII-induced proliferation of vascular smooth muscle cells. 1868 7

Ca(2+) is a pivotal signal in human pulmonary artery smooth muscle cells (PASMCs) proliferation. Capacitative Ca(2+) entry (CCE) via the store-operated channel (SOC), which encoded by the transient receptor potential (TRP) gene, is an important mechanism for regulating intracellular Ca(2+) concentration ([Ca(2+)](i)) in PASMCs. Sildenafil, a potent type 5 nucleotide-dependent phosphodiesterase (PDE) inhibitor, has been proposed as a therapeutic tool to treat or prevent pulmonary arterial hypertension (PAH); however, the mechanism of its antiproliferative effect on PASMCs remains unclear. This study was designed to investigate the possible antiproliferative mechanism of sildenafil on human PASMCs, namely, its effect on the Ca(2+)-signal pathway. Cultured normal PASMCs were treated with endothelin-1 (ET-1) or ET-1 plus sildenafil separately. Cell number and viability were determined with a hemocytometer or MTT assay. [Ca(2+)](i) was measured by loading PASMCs with fura 2-AM. Expression of the TRPC1 gene and protein was detected by RT-PCR and Western blot, respectively. The results show that sildenafil dose-dependently inhibited the proliferation of PASMCs, the enhancement of basal [Ca(2+)](i) level, increase of CCE, and upregulation of TRPC expression induced by ET-1. These results suggest that sildenafil potently inhibits ET-1-induced PASMCs proliferation and downregulation of CCE and TRPC expression may be responsible for its antiproliferative effect.
 ...
PMID:Sildenafil inhibits human pulmonary artery smooth muscle cell proliferation by decreasing capacitative Ca2+ entry. 1881 82

Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) plays a critical role in the development of pulmonary artery hypertension, and inhibition of PASMC proliferation has been shown to be beneficial to patients with this disease. Recent studies indicate that Rho/ROCK is critically involved in the proliferation of smooth muscle cells. However, the signal transduction of Rho/ROCK and its downstream signaling are not fully understood. In the present study, we investigated the antiproliferation effect of fasudil hydrochloride hydrate, a Rho-kinase inhibitor, on rat PASMC proliferation, and the possible relation of Rho/ROCK to ERK, JNK pathways. The results indicate that fasudil effectively inhibited 5-HT-induced PASMC proliferation, as evaluated by MTT assay and protein expression of proliferating cell nuclear antigen. Flow cytometry analysis showed that fasudil markedly blocked 5-HT-induced cell-cycle progression by arresting the cells in the G(0)/G(1) phase. Consistently, 5-HT-induced ROCK-1 mRNA expression and MYPT-1 phosphorylation were markedly suppressed by fasudil. In addition, fasudil significantly decreased 5-HT-induced JNK activation, ERK translocation to the nucleus and subsequent c-fos and c-jun expression. Taken together, these results indicate that Rho/ROCK is essential for PASMC proliferation produced by 5-HT. Fasudil effectively suppressed 5-HT-induced PASMC proliferation and cell-cycle progression, which was associated with inhibition of JNK activation, ERK translocation to nucleus and subsequent c-fos and c-jun expression.
 ...
PMID:Fasudil hydrochloride hydrate, a Rho-kinase inhibitor, suppresses 5-hydroxytryptamine-induced pulmonary artery smooth muscle cell proliferation via JNK and ERK1/2 pathway. 1905 84

To examine the changes in number and function of endothelial progenitor cells (EPCs) from peripheral blood (PB) in hypertension disorder complicating pregnancy (HDCP), 20 women with HDCP and 20 normal pregnant women at the third trimester were studied. Mononuclear cells (MNCs) from PB were isolated by Ficoll density gradient centrifugation. EPCs were identified by positive expression of both CD34 and CD133 under fluorescence microscope and positive expression of factor VIII as shown by immunocytochemistry. The number of EPCs was flow-cytometrically determined. Proliferation and migration of EPCs were measured by MTT assay and modified Boyden chamber assay, respectively. The adhesion activity of EPCs was detected by counting the number of the adherent cells. The results showed that, compared with normal pregnant women, the number of EPCs was significantly reduced in HDCP (4.29%+/-1.21% vs 15.32%+/-2.00%, P<0.01), the functional activity of EPCs in HDCP, such as proliferation (13.45%+/-1.68% vs 18.45%+/-1.67%), migration (37.25+/-7.28 cells/field vs 67.10+/-9.55 cells/field) and adhesion activity (20.65+/-5.19 cells/field vs 34.40+/-6.72 cells/filed) was impaired (P<0.01). It is concluded that the number and function of EPCs are significantly decreased in HDCP.
 ...
PMID:Changes in number and biological function of endothelial progenitor cells in hypertension disorder complicating pregnancy. 1910 63


1 2 3 4 5 6 7 Next >>