Vascular smooth muscle cell calcium fluxes. Regulation by angiotensin II and lipoproteins.

Orlov, Sergei N.; Resink, Thérèse J.; Bernhardt, J.; Ferracin, Fabrizia; Bühler, Fritz R.

doi:10.1161/01.hyp.21.2.195

Cited by 50 publications

(16 citation statements)

References 53 publications

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“…Second, neither [Ca 2+ ] i nor total exchangeable Ca content in VSMC is affected by ouabain [109]. This observation is consistent with negligible Na + /Ca 2+ exchanger activity detected in VSMC [117]. Third, neither the omission of Ca 2+ o nor the addition of extracellular (EGTA) and intracellular (BAPTA-AM) Ca 2+ chelators abolishes ouabaininduced c-Fos expression [109].…”

Section: Iv3 Expression Of Na + I -Sensitive Genes Is Mediated By Asupporting

confidence: 57%

Cardiotonic Steroids: Novel Mechanisms of Na+ i-Mediated and - Independent Signaling Involved in the Regulation of Gene Expression, Proliferation and Cell Death

Orlov¹,

Akimova²,

Hamet

2005

CHYR

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Vascular remodeling and hypertrophy/hyperplasia of the heart and kidney are known to be major servomechanisms of long-term maintenance of elevated blood pressure and the development of cardiovascular and renal complications seen in hypertension. Several lines of evidence suggest that these abnormalities are genetically determined and evoke an imbalance between cell proliferation and death. During the last 2 decades, it was shown that the level of cardiotonic steroids (CTS), i.e. potent and selective Na + ,K + -ATPase inhibitors, is increased in several forms of volumeexpanded hypertension. We focus our review on recent data implicating CTS in the regulation of cell proliferation and death. At low concentrations, CTS augment proliferation of vascular smooth muscle cells (VSMC) as well as renal epithelial and vascular endothelial cells without significant inhibition of Na + ,K + -ATPase-mediated ion fluxes. In contrast to cell proliferation, effect of CTS on cell survival is tissue-specific. In VSMC, CTS inhibit programmed cell death via a novel Na + i -mediated, Ca 2+ i -independent mechanism of expression of antiapoptotic genes including mortalin, whereas in vascular endothelial and renal epithelial cells, long-term exposure to CTS leads to cell death showing combined markers of apoptosis and necrosis. This mode of cell death is caused by interaction of CTS with Na + ,K + -ATPase but is independent of inhibition of the Na + ,K + -ATPase-mediated ion fluxes and inversion of the [Na + ] i /[K + ] i ratio. We propose that these novel signaling pathways triggered by enhanced production of endogenous CTS and/or abnormal Na + handling contribute to cardiovascular and renal complications seen in hypertension.

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Section: Iv3 Expression Of Na + I -Sensitive Genes Is Mediated By Asupporting

confidence: 57%

Cardiotonic Steroids: Novel Mechanisms of Na+ i-Mediated and - Independent Signaling Involved in the Regulation of Gene Expression, Proliferation and Cell Death

Orlov¹,

Akimova²,

Hamet

2005

CHYR

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“…Increased activation of these channels has been implicated in enhanced vascular contractility and structural alterations in hypertension. 45,46 MEK could also influence contraction by changing pH i . Ang II-induced intracellular alkalinization, a consequence of activation of the Na ϩ -H ϩ exchanger, increases Ca 2ϩ sensitivity of the actin-myosin complex, thereby modulating the contractile properties of vascular smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

Mitogen-Activated Protein/Extracellular Signal–Regulated Kinase Inhibition Attenuates Angiotensin II–Mediated Signaling and Contraction in Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells

Touyz

Mabrouk

et al. 1999

Circulation Research

140

104

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Abstract-This study investigates the role of extracellular signal-regulated kinases (ERKs) ] i (E max , 294Ϯ55 nmol/L) and pH i (E max , 7.27Ϯ0.04) effects were significantly reduced by PD98059 in SHR. Ang II-induced ERK activity was significantly greater (PϽ0.05) in SHR than in WKY. In conclusion, Ang II-stimulated signal transduction and associated VSMC contraction are enhanced in SHR. MAP/ERK inhibition abrogated sustained contraction and normalized Ang II effects in SHR. These data suggest that ERK-dependent signaling pathways influence contraction and that they play a role in vascular hyperresponsiveness in SHR. (Circ Res. 1999;84:505-515.) Key Words: [Ca 2ϩ ] i Ⅲ pH i Ⅲ resistance vessel Ⅲ PD98059 Ⅲ hypertension I ncreased peripheral resistance plays a critical role in blood pressure elevation. In spontaneously hypertensive rats (SHR), this increase in vascular resistance has been attributed to multiple interacting factors, including structural alterations in small vessels, decreased endothelium-dependent vasodilation, and enhanced vascular reactivity to vasoconstrictor stimuli. 1 Of the many vasoactive agonists that have been implicated in vascular hyperresponsiveness in hypertension, angiotensin II (Ang II) appears to play one of the most important roles. Whereas responses to endothelin-1, vasopressin, and norepinephrine have been reported to be decreased, unchanged, or (rarely) increased, vascular reactivity to Ang II has, for the most part, been found to be increased in vessels from adult SHR. 2-4 Altered Ang II-stimulated vascular responsiveness occurs early in the development of hypertension, and we and others have shown increased intracellular free Ca 2ϩ concentration ([Ca 2ϩ ] i ) and contractile effects of Ang II in SHR as young as 6 weeks of age. 5,6 Ang IImediated vascular hyperresponsiveness is not specific to SHR, as similar Ang II-related actions, both in the prehypertensive and established hypertensive phases, have been demonstrated in other models of hypertension, including strokeprone SHR, renal hypertensive rats, and desoxycorticosterone acetate/salt-hypertensive rats. [7][8][9] The signal transduction systems responsible for enhanced Ang II-elicited excitation-contraction coupling in hypertension are not completely understood, and the signaling processes involved in the prehypertensive phase may differ from

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“…10 ' 11 Cytosolic calcium overload has been demonstrated in many cell types, including platelets, from hypertensive patients and genetic and experimental hypertensive rats.…”

mentioning

confidence: 99%

Effects of angiotensin II and endothelin-1 on platelet aggregation and cytosolic pH and free Ca2+ concentrations in essential hypertension.

Touyz

Schiffrin

1993

Hypertension

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The aims of this study were to determine the relations between platelet free calcium concentrations ([Ca 2+ D, intracellular pH (pH,), and aggregation and to assess the effects of angiotensin II (Ang II) and endothelin-1 on these platelet parameters in normotensive subjects and hypertensive patients. Seventeen normotensive subjects, 25 untreated hypertensive patients, and 34 treated hypertensive patients were studied. Platelet cytosolic free [Ca 3+ ]| and pH, were measured spectrofluorometrically using specific fluorescent probes (fura 2-AM and BCECF-AM, respectively) in unstimulated and Ang II-and endothelin-1-stimulated platelets. Aggregation was measured by a turbidometric technique. Basal [Ca 2+ ], (141±11 nmol/L) and pH (7.16±0.01) were higher (P<.05) in the untreated hypertensive group compared with the normotensive (118±9 nmol/L, 7.11±0.01, respectively) and treated hypertensive (121±11 nmol/L, 7.12±0.01, respectively) groups. In the combined normotensive and hypertensive groups, there were significant correlations between [ ]; induced by Ang II was significantly higher (P<.05) in the untreated hypertensive group compared with the other groups (67±6 nmol/L for the untreated hypertensive group versus 54±5 and 29±8 nmol/L for the normotensive and treated hypertensive groups, respectively). In the presence of Ang II, thrombin-induced aggregatory responses were increased in all three groups, but the maximal response was significantly higher in the untreated hypertensive group compared with the other groups (P<.05). Endothelin-1 increased pH, through endothelin A-receptors (effect blocked by the specific antagonist BQ-123) but had no significant effect on lCa 2+ ], or aggregation. However, endothelin-1 blunted thrombin-induced platelet aggregation in normotensive subjects but not in hypertensive patients. In conclusion, increased Ang H-stimulated [Ca 2+ j| and pH, in platelets of essential hypertensive patients may be associated with increased aggregatory responses. The stimulatory effect of endothelin-1 on pH, but not on [Ca 2+ ], or aggregation suggests that in platelets endothelin-induced signaling pathways other than phospholipase C may be involved. The significant correlations between platelet aggregation, [Ca 2+ L, pH,, and blood pressure may suggest a possible link between altered platelet cation status and platelet function in hypertension. (Hypertension. 1993;22:853-862 12 Cytosolic free calcium regulates many cellular processes, including tone, contractility, and reactivity in vascular smooth muscle cells and activation, aggregation, and adhesion in platelets.

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Vascular smooth muscle cell calcium fluxes. Regulation by angiotensin II and lipoproteins.

Cited by 50 publications

References 53 publications

Cardiotonic Steroids: Novel Mechanisms of Na+ i-Mediated and - Independent Signaling Involved in the Regulation of Gene Expression, Proliferation and Cell Death

Cardiotonic Steroids: Novel Mechanisms of Na+ i-Mediated and - Independent Signaling Involved in the Regulation of Gene Expression, Proliferation and Cell Death

Mitogen-Activated Protein/Extracellular Signal–Regulated Kinase Inhibition Attenuates Angiotensin II–Mediated Signaling and Contraction in Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells

Effects of angiotensin II and endothelin-1 on platelet aggregation and cytosolic pH and free Ca2+ concentrations in essential hypertension.

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