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

Oxidative stress was reported to be involved not only in cardiovascular diseases, but also in hypertension. Epidemiologic studies indicated that tea consumption slightly reduces blood pressure. We conducted two studies to determine whether black and green tea can lower blood pressure (BP) in stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP (n=15) were allowed to recover for 2 wk after a transmitter for measuring BP was implanted in the peritoneal cavity. The rats were divided into three groups: the control group consumed tap water (30 mL/d); the black tea polyphenol group (BTP) consumed water containing 3.5 g/L thearubigins, 0.6 g/L theaflavins, 0.5 g/L flavonols and 0.4 g/L catechins; and the green tea polyphenol group (GTP) consumed water containing 3.5 g/L catechins, 0.5 g/L flavonols and 1 g/L polymetric flavonoids. The telemetry system was used to measure BP, which were recorded continuously every 5 min for 24 h. During the daytime, systolic and diastolic BP were significantly lower in the BTP and GTP groups than in the controls. Protein expressions of catalase and phosphorylated myosin light chain (MLC-p) were measured in the aorta by Western blotting. GTP significantly increased catalase expression, and BTP and GTP significantly decreased MLC-p expression in the aorta. These data demonstrate that both black and green tea polyphenols attenuate blood pressure increases through their antioxidant properties in SHRSP. Furthermore, because the amounts of polyphenols used in this experiment correspond to those in approximately 1 L of tea, the regular consumption of black and green tea may also provide some protection against hypertension in humans.
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PMID:Black and green tea polyphenols attenuate blood pressure increases in stroke-prone spontaneously hypertensive rats. 1470 90

The serine/threonine protein kinase Rho kinase, a downstream effector of the small GTPase Rho, regulates actin cytoskeletal organization, cell adhesion, cell motility, smooth muscle contraction and gene expression. Rho kinase constitutes the essential regulatory system for myosin phosphatase, controlling myosin light chain phosphorylation and thereby vascular tone. Inhibitors of Rho kinase were shown to be effective in ameliorating hypertension, vasospasm, vascular injury and associated organ damages in various animal disease models. These recent observations imply potential usefulness of the Rho kinase inhibitors as novel therapeutic and preventive agents for vascular disorders and accompanying organ injury.
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PMID:[Rho-Rho kinase pathway]. 1473 34

Although human heme oxygenase-1 (hHO-1) could provide a useful approach for cellular protection in the ischemic heart, constitutive overexpression of hHO-1 may lead to unwanted side effects. To avoid this, we designed a hypoxia-regulated hHO-1 gene therapy system that can be switched on and off. This vigilant plasmid system is composed of myosin light chain-2v promoter and a gene switch that is based on an oxygen-dependent degradation domain from the hypoxia inducible factor-1-alpha. The vector can sense ischemia and switch on the hHO-1 gene system, specifically in the heart. In an in vivo experiment, the vigilant hHO-1 plasmid or saline was injected intramyocardially into myocardial infarction mice or sham operation mice. After gene transfer, expression of hHO-1 was only detected in the ischemic heart treated with vigilant hHO-1 plasmids. Masson trichrome staining showed significantly fewer fibrotic areas in vigilant hHO-1 plasmids-treated mice compared with saline control (43.0%+/-4.8% versus 62.5%+/-3.3%, P<0.01). The reduction of interstitial fibrosis is accompanied by an increase in myocardial hHO-1 expression in peri-infarct border areas, concomitant with higher Bcl-2 levels and lower Bax, Bak, and caspase 3 levels in the ischemic myocardium compared with saline control. By use of a cardiac catheter, heart from vigilant hHO-1 plasmids-treated mice showed improved recovery of contractile and diastolic performance after myocardial infarction compared with saline control. This study documents the beneficial regulation and therapeutic potential of vigilant plasmid-mediated hHO-1 gene transfer. This novel gene transfer strategy can provide cardiac-specific protection from future repeated bouts of ischemic injury.
Hypertension 2004 Apr
PMID:Protection from ischemic heart injury by a vigilant heme oxygenase-1 plasmid system. 1496 35

Diminished insulin (Ins) sensitivity is a characteristic feature of various pathological conditions such as the cardiometabolic syndrome, Type 2 diabetes, and hypertension. Persons with essential hypertension are more prone than normotensive persons to develop diabetes, and this propensity may reflect decreased ability of Ins to promote relaxation and glucose transport in vascular and skeletal muscle tissue, respectively. There are increasing data suggesting that ANG II acting through its ANG type 1 receptor inhibits the actions of Ins in vascular and skeletal muscle tissue, in part, by interfering with Ins signally through phosphatidylinositol 3-kinase (PI3K) and its downstream protein kinase B (Akt) signaling pathways. This inhibitory action of ANG II is mediated, in part, through stimulation of RhoA activity and oxidative stress. Activated RhoA and increased reactive oxygen species inhibition of PI3K/Akt signaling results in decreased endothelial cell production of nitric oxide, increased myosin light chain activation with vasoconstriction, and reduced skeletal muscle glucose transport.
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PMID:Insulin resistance and hypertension. 1507 67

Phosphorylation of the RMLC (regulatory myosin light chain) regulates the activity of myosin II, which is critically involved in the motility of both muscle and non-muscle cells. There are both Ca2+-dependent and -independent pathways for RMLC phosphorylation in smooth-muscle cells, and the latter pathway is often involved in an abnormal contractility in pathological states such as asthma and hypertension. Therefore pharmacological interventions of RMLC phosphorylation may have a therapeutic value. In the present study, we developed a new genetically encoded biosensor, termed CRCit (ECFP-RMLC-Citrine, where ECFP is enhanced cyan fluorescent protein), that detects RMLC phosphorylation using fluorescence resonance energy transfer between two variants of the green fluorescent protein fused to both the N- and C-termini of RMLC. When expressed in primary cultured vascular smooth-muscle cells, CRCit detected the Ca2+-dependent RMLC phosphorylation with a high spatiotemporal resolution. Furthermore, we could specifically assay the agonist-induced Ca2+-independent phosphorylation of RMLC when Ca2+ signalling in cells expressing CRCit was suppressed. Thus CRCit may also be used for the high throughput screening of compounds that inhibit abnormal smooth-muscle contraction.
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PMID:Real-time imaging of myosin II regulatory light-chain phosphorylation using a new protein biosensor. 1536 55

Evidence indicates that both the Rho/Rho kinase signaling pathway and reactive oxygen species (ROS) such as superoxide and H(2)O(2) are involved in the pathogenesis of hypertension. This study aimed to determine whether ROS-induced vascular contraction is mediated through activation of Rho/Rho kinase. Rat aortic rings (endothelium denuded) were isolated and placed in organ chambers for measurement of isometric force development. ROS were generated by a xanthine (X)-xanthine oxidase (XO) mixture. The antioxidants tempol (3 mM) and catalase (1,200 U/ml) or the XO inhibitor allopurinol (400 microM) significantly reduced X/XO-induced contraction. A Rho kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl-N-4-pyridil)cyclohexanecarboxamide dihydrochloride (Y-27632), decreased the contraction in a concentration-dependent manner; however, the Ca(2+)-independent protein kinase C inhibitor rottlerin did not have an effect on X/XO-induced contraction. Phosphorylation of the myosin light chain phosphatase target subunit (MYPT1) was increased by ROS, and preincubation with Y-27632 blocked this increased phosphorylation. Western blotting for cytosolic and membrane-bound fractions of Rho showed that Rho was increased in the membrane fraction by ROS, suggesting activation of Rho. These observations demonstrate that ROS-induced Ca(2+) sensitization is through activation of Rho and a subsequent increase in Rho kinase activity but not Ca(2+)-independent PKC.
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PMID:Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta. 1537 Dec 61

Epidemiological studies link intra-uterine growth restriction (IUGR) with increased incidence of hypertension and cardiac disease in adulthood. Our rat model of IUGR supports this contention and provides evidence for the programming of susceptibility for hypertension in all offspring. Moreover, in the female offspring only, gross anatomical changes (cardiac ventricle to body ratios) and increased left cardiac ventricular atrial natriuretic peptide (ANP) mRNA levels provide evidence for programming of cardiac disease in this gender. The aim of the current study was to measure changes in cardiac tissue that support remodelling that could be implicated in the initiation of hypertrophy. Adult female rats from our IUGR model and age- and sex-matched controls were killed at 12 weeks of age. Left cardiac ventricles were removed and used for monitoring changes in several key genes, Na+,K+-ATPase beta1 protein expression, cardiomyocyte morphology and contractility as well as citrate synthase and aconitase activities. When compared to controls, female offspring of our IUGR rat model exhibit higher expression (mRNA) of ANP and the atrial isoform of the myosin light chain, lower levels of Na+,K+-ATPase beta1 protein, increased cardiomyocyte depth and volume, increased sarcomere length, diminished cardiomyocyte contractility and lower aconitase activity. Female offspring of our IUGR rat model exhibit changes as adults that are consistent with the onset of cardiac remodelling. The decrease in aconitase activity suggests that oxidative stress may be implicated in this response.
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PMID:Intra-uterine growth restriction and the programming of left ventricular remodelling in female rats. 1577 37

Dynamic remodeling of the actin cytoskeleton occurs during agonist-induced smooth muscle contraction. Tyrosine phosphorylation of the adaptor protein paxillin has been implicated in regulation of actin filament formation and force development. We have investigated the role of the actin cytoskeleton in noradrenaline (NA)-induced and endothelin (ET)-induced activation of the calcium-dependent nonreceptor tyrosine kinase PYK2 and subsequent phosphorylation of paxillin in rat small mesenteric arteries. NA and ET induced a rapid and prolonged activation of PYK2, as shown by increased phosphorylation at Y402 and Y881, and a concomitant association of the kinase with a Triton X-100 insoluble membrane (cytoskeleton) compartment. Both agonists also increased phosphorylation of paxillin at Y31 and Y118 with a similar time course as PYK2 phosphorylation, and induced its association with the same membrane compartment as PYK2. Treatment of arteries with cytochalasin D disrupted stress fibers and inhibited NA-induced and ET-induced force in a myosin light chain 20 phosphorylation independent and reversible manner. However, cytochalasin D treatment had no effect on NA-induced and ET-induced phosphorylation of either PYK2 or paxillin but did prevent their association with the TritonX-100 insoluble membrane compartment. These results show that in mesenteric arteries an intact cytoskeleton and force development are not prerequisites for G-protein--coupled receptor--induced activation of PYK2 and paxillin, by tyrosine phosphorylation, in vascular tissue, but are necessary for the translocation of PYK2 and paxillin to the membrane.
Hypertension 2005 Jul
PMID:Role of the actin cytoskeleton in G-protein-coupled receptor activation of PYK2 and paxillin in vascular smooth muscle. 1591 46

The small guanosine triphosphatase Rho and its target, Rho kinase, play important roles in both blood pressure regulation and vascular smooth muscle contraction. Rho is activated by agonists of receptors coupled to cell membrane G protein, such as angiotensin II and phenylephrine. Once Rho is activated, it translocates to the cell membrane where it, in turn, activates Rho kinase. Activated Rho kinase phosphorylates myosin light chain phosphatase, which is then inhibited. This sequence stimulates vascular smooth muscle contraction, stress fiber formation,and cell migration. In this way, Rho and Rho kinase activation have important effects on several cardiovascular diseases. Currently available substances that specifically inhibit this signaling pathway could offer clinical benefits in several cardiovascular, as well as noncardiovascular diseases, such as arterial hypertension, pulmonary hypertension, cerebral or coronary spasm, post-angioplasty restenosis, and erectile dysfunction.
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PMID:[Rho/Rho kinase signal transduction pathway in cardiovascular disease and cardiovascular remodeling]. 1605 29

Vascular contraction is an important determinant of the peripheral vascular resistance and blood pressure. The mechanisms underlying vascular smooth muscle (VSM) contraction and the pathological changes that occur in hypertension have been the subject of numerous studies and interpretations. Activation of VSM by vasoconstrictor stimuli at the cell surface causes an increase in [Ca(2+)](i), Ca(2+)-dependent activation of myosin light chain (MLC) kinase, MLC phosphorylation, actin-myosin interaction and VSM contraction. Additional signaling pathways involving Rho-kinase and protein kinase C (PKC) may increase the myofilament force sensitivity to [Ca(2+)](i) and MLC phosphorylation, and thereby maintain vascular contraction. PKC is a particularly intriguing protein kinase as it comprises a family of Ca(2+)-dependent and Ca(2+)-independent isoforms, which have different tissue and subcellular distribution, and undergo differential translocation during cell activation. PKC translocation to the cell surface may trigger a cascade of protein kinases, such as mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK) that ultimately interact with the contractile myofilaments and cause VSM contraction. Also, PKC translocation to the nucleus may promote VSM growth and proliferation. Increased PKC expression and activity have been identified in several forms of hypertension. The subcellular location of PKC may determine the state of VSM activity, and may be useful in the diagnosis/prognosis of hypertension. Vascular PKC isoforms may represent specific targets for modulation of VSM hyperactivity, and isoform-specific PKC inhibitors may be useful in treatment of Ca(2+) antagonist-resistant forms of hypertension.
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PMID:Protein kinase C isoforms as specific targets for modulation of vascular smooth muscle function in hypertension. 1613 52


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