Calcium handling by vascular myocytes in hypertension

Tostes, Rita C.; Wilde, Dixon W.; Bendhack, Lusiane Maria; Webb, R. Clinton

doi:10.1590/s0100-879x1997000300004

Cited by 27 publications

(16 citation statements)

References 49 publications

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“…Smooth muscle cells and isolated vascular tissue from SHR and DOCA-salt rats have been shown to have greater basal and agonist-induced intracellular calcium concentrations, as well as heightened sensitivity to the calcium channel agonist Bay K 8644, possibly mediated by an increased activity of voltage gated Ca ++ channels [27][28][29]. An increased response to depolarization stimuli (potassium chloride) in isolated tissue also supports the role of altered Ca ++ channels in hypertension.…”

Section: Increased Vasoconstrictor Sensitivity In Hypertensionmentioning

confidence: 84%

RhoA/Rho-kinase, vascular changes, and hypertension

Chitaley

Weber

Webb

2001

Current Science Inc

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Hypertension, the result of a sustained increase in vascular peripheral resistance, is partly due to vascular remodeling and increased vasoconstrictor sensitivity. Stimulation of heterotrimeric G-protein-coupled receptors by various contractile agonists activates intracellular signaling molecules to result in an increase in cytosolic Ca++ and the subsequent phosphorylation of myosin light chain by Ca++/calmodulin-dependent myosin light chain kinase. Additionally, a portion of alpha-adrenergic, serotonergic, and endothelin-1-induced contraction is partially mediated by the calcium-independent activation of the small G-protein RhoA and of a downstream target, Rho-kinase. Isolated arteries from hypertensive animals have been shown to have an increased contractile sensitivity to various agonists and to exhibit evidence of remodeling. Recent data suggest that some of these vascular changes may be mediated by increased activity of RhoA/Rho-kinase, potentially introducing a novel therapeutic approach for the treatment of hypertension.

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Section: Increased Vasoconstrictor Sensitivity In Hypertensionmentioning

confidence: 84%

RhoA/Rho-kinase, vascular changes, and hypertension

Chitaley

Weber

Webb

2001

Current Science Inc

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“…In the current study we investigated whether the increased ET-1/ET B receptormediated vascular responses observed in male, but not in female, DOCA-salt rats are associated with gender differences in the vascular mRNA expression of ET-1 and ET A / ET B receptors and/or with functional differences in Ca 2+ handling mechanisms by vascular myocytes. The rationale was based on the observations that i) changes in both receptor function or intracellular Ca 2+ regulation are implicated in altered vascular reactivity in hypertension; ii) a defect in intracellular Ca 2+ regulation, characterized by increased basal tone, increased L-type Ca 2+ channel activity and altered mobilization of Ca 2+ from intracellular stores, has been extensively described in the vasculature of male DOCA-salt hypertensive rats (11,12,15); iii) ET-1 has been shown to exert a wide range of effects on some of these defective mechanisms, activating Ca 2+ influx mainly through VOC and also stimulating IP 3 -dependent and (to a lesser extent) IP 3 -independent Ca 2+ release from intracellular stores (3-5); …”

Section: Discussionmentioning

confidence: 99%

Gender differences in vascular expression of endothelin and ET A/ET B receptors, but not in calcium handling mechanisms, in deoxycorticosterone acetate-salt hypertension

David

Montezano

Rebouças

et al. 2002

Braz J Med Biol Res

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We determined if the increased vascular responsiveness to endothelin-1 (ET-1) observed in male, but not in female, DOCA-salt rats is associated with differential vascular mRNA expression of ET-1 and/ or ET A /ET B receptors or with functional differences in Ca 2+ handling mechanisms by vascular myocytes. Uninephrectomized male and female Wistar rats received DOCA and drinking water containing NaCl/KCl. Control rats received vehicle and tap water. Blood pressure and contractile responses of endothelium-denuded aortic rings to agents which induce Ca 2+ influx and/or its release from internal stores were measured using standard procedures. Expression of mRNA for ET-1 and ET A /ET B receptors was evaluated by RT-PCR after isolation of total cell RNA from both aorta and mesenteric arteries. Systolic blood pressure was higher in male than in female DOCA rats. Contractions induced by Bay K8644 (which activates Ca 2+ influx through voltage-operated L-type channels), and by caffeine, serotonin or ET-1 in Ca 2+ -free buffer (which reflect Ca 2+ release from internal stores) were significantly increased in aortas from male and female DOCAsalt compared to control aortas. DOCA-salt treatment of male, but not female, rats statistically increased vascular mRNA expression of ET-1 and ET B receptors, but decreased the expression of ET A receptors. Molecular up-regulation of vascular ET B receptors, rather than differential changes in smooth muscle Ca 2+ handling mechanisms, seems to account for the increased vascular reactivity to ET-1/ET B receptor agonists and higher blood pressure levels observed in male DOCA-salt rats.

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“…Vascular contraction to ET-1 is increased in rat hearts during ischemia/ reperfusion and in the rat pulmonary circulation in pulmonary hypertension [46]. Evidence indicates that a defect in VSM regulation of intracellular Ca 2+ may play a role in the augmented vascular reactivity to ET-1 in some forms of experimental hypertension [65,79]. However, vascular contraction to ET is unchanged in the aorta of SHR and is even decreased in the mesenteric arteries of DOCA-salt hypertensive rats [46,64].…”

Section: Vascular Response To Et In Hypertensionmentioning

confidence: 99%

The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

Hynynen

Khalil²

2006

PRC

103

105

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The discovery of endothelin two decades ago has now evolved into an intricate vascular endothelin (ET) system. Several ET isoforms, receptors, signaling pathways, agonists, antagonists, and clinical applications have been identified and documented in first-rate patents. The role of ET as one of the most potent endothelium-derived vasoconstricting factors is now complemented by a newly discovered role in vascular relaxation. ET synthesis is initiated by the transcription of ET genes in endothelial cells and the generation of the gene products preproET and big ET, which are further cleaved by specific ET converting enzymes into ET-1, -2, -3 and -4 isoforms. ET isoforms bind with different affinities to ET A and ET B2 receptors in vascular smooth muscle, and stimulate [Ca 2+ ] i , protein kinase C, mitogen-activated protein kinase and other signaling mechanisms of smooth muscle contraction, growth and proliferation. ET also binds to endothelial ET B1 receptors, which mediate the release of vasodilator substances such as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor. Endothelial ET B1 receptors may also function in ET re-uptake and clearance. Although the effects of ET on vascular function and growth are well-recognized, the role of ET and its receptors in the regulation of blood pressure and in the pathogenesis of hypertension is not clearly established. Salt-dependent hypertension in experimental animals and some forms of moderate to severe hypertension in human may show elevated levels of plasma or vascular ET; however, other forms of hypertension show normal ET levels. The currently available ET receptor antagonists reduce blood pressure in some forms of experimental hypertension. Careful examination of recent patents may identify more effective and specific modulators of the vascular ET system for clinical use in human hypertension.

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Calcium handling by vascular myocytes in hypertension

Cited by 27 publications

References 49 publications

RhoA/Rho-kinase, vascular changes, and hypertension

RhoA/Rho-kinase, vascular changes, and hypertension

Gender differences in vascular expression of endothelin and ET A/ET B receptors, but not in calcium handling mechanisms, in deoxycorticosterone acetate-salt hypertension

The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

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