Protective Action of Indapamide, a Thiazide-Like Diuretic, on Ischemia-Induced Injury and Barrier Dysfunction in Mouse Brain Microvascular Endothelial Cells

Nishioku, Tsuyoshi; Takata, Fuyuko; Yamauchi, Atsushi; Sumi, Noriko; Yamamoto, I.; Fujino, Akiko; Naito, Mikihiko; Tsuruo, Takashi; Shuto, Hideki; Kataoka, Yasufumi

doi:10.1254/jphs.sc0060222

Cited by 18 publications

(12 citation statements)

References 15 publications

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“…Other in vitro studies have demonstrated that hypoxia with reoxygenation increases endothelial cell permeability (Utepbergenov et al 1998;Dohgu et al 2007;Nishioku et al 2007). Fig.…”

Section: Discussionmentioning

confidence: 96%

Tissue Plasminogen Activator Enhances the Hypoxia/reoxygenation-induced Impairment of the Blood–brain Barrier in a Primary Culture of Rat Brain Endothelial Cells

et al. 2008

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Hemorrhagic transformation is a major complication associated with tissue plasminogen activator (tPA) therapy for ischemic stroke. We studied the effect of tPA on the blood-brain barrier (BBB) function with our in vitro monolayer model generated using rat brain microvascular endothelial cells subjected either to normoxia or to hypoxia/reoxygenation (H/R) with or without the administration of tPA. The barrier function was evaluated by the transendothelial electrical resistance (TEER), the permeability of sodium fluorescein and Evans' blue-albumin (EBA), and the uptake of lucifer yellow (LY). The permeability of sodium fluorescein and EBA was used as an index of paracellular and transcellular transport, respectively. The administration of tPA increased the permeability of EBA and the uptake of LY under normoxia. It enhanced the increase in the permeability of both sodium fluorescein and EBA, the decrease in the TEER, and the disruption in the expression of ZO-1 under H/R conditions. Administration of tPA could cause an increase in the transcellular transport under normoxia, and both the transcellular and paracellular transport of the BBB under H/R conditions in vitro. Even in humans, tPA may lead to an opening of the BBB under non-ischemic conditions and have an additional effect on the ischemia-induced BBB disruption.

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“…Other in vitro studies have demonstrated that hypoxia with reoxygenation increases endothelial cell permeability (Utepbergenov et al 1998;Dohgu et al 2007;Nishioku et al 2007). Fig.…”

Section: Discussionmentioning

confidence: 96%

Tissue Plasminogen Activator Enhances the Hypoxia/reoxygenation-induced Impairment of the Blood–brain Barrier in a Primary Culture of Rat Brain Endothelial Cells

et al. 2008

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“…16,17,33 All these effects are probably mediated by inhibition of CAs present in blood vessels or in the kidneys, but no specific pharmacological or biochemical studies are available so far, except for these clinical observations mentioned here. [28][29][30][31][32][33] The lesson we learned from all these data is that probably many of the recently reported beneficial clinical properties of indapamide 6.10 are indeed due to its diuretic effects, but in conjunction with its strong inhibition of some CA isozymes (such as CA IV, VB, VII, IX, XII, and/or XIII) reported here for the first time, isoforms present in kidneys and blood vessels. This hypothesis may explain both the blood pressure lowering effects and organprotective activity of the drug.…”

Section: Potential Novel Applications Of the Diuretic Sulfonamides Inmentioning

confidence: 78%

“…[25][26][27][28][29][30] In line with these studies, 25-30 a very recent report shows that indapamide 6.10 has a protective role against ischemia-induced injury and dysfunction of the blood-brain barrier, probably due to its vasodilating effects. 31,32 An organ-protective effect of indapamide in animal models of renal failure has also been reported, showing the drug to be beneficial in preventing damage to the capillary structures, the endothelium, and in reducing the hypertrophy of superficial glomeruli among others. 16,17,33 All these effects are probably mediated by inhibition of CAs present in blood vessels or in the kidneys, but no specific pharmacological or biochemical studies are available so far, except for these clinical observations mentioned here.…”

Section: Potential Novel Applications Of the Diuretic Sulfonamides Inmentioning

confidence: 97%

Diuretics with Carbonic Anhydrase Inhibitory Activity: Toward Novel Applications for Sulfonamide Drugs

Vullo

Innocenti

Supuran

2009

Drug Design of Zinc‐Enzyme Inhibitors

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“…Interestingly, indapamide, a thiazide that strongly inhibits carbonic anhydrase, has also been shown to inhibit vascular permeability induced by ischemia in brain capillary cells. 27 In those studies, the cells were not cultured with the addition of exogenous VEGF. The baseline permeability of Evans blue-labeled albumin across our cultured endothelial cells was 250% greater (data not shown) than baseline permeability of the cultured VSMCs.…”

Section: Discussionmentioning

confidence: 99%

Chlorthalidone Decreases Platelet Aggregation and Vascular Permeability and Promotes Angiogenesis

2010

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Abstract-Variations in diuretic-mediated inhibition of carbonic anhydrase-dependent chloride transport in platelets and vascular smooth muscle could account for the contrasting efficacy of the thiazide and thiazide-like diuretics in reducing cardiovascular morbidity in patients with hypertension. We assessed platelet carbonic anhydrase activity and catecholamine-induced platelet aggregation in the presence of a thiazide and a "thiazide-like" inhibitor of the sodium-chloride cotransporter. Individual variation in platelet carbonic anhydrase activity correlated with contrasting sensitivity to epinephrine-mediated platelet aggregation. Both chlorthalidone, which potently inhibits platelet carbonic anhydrase, and bendroflumethiazide, which has much less effect on this enzyme, increased the amount of epinephrine needed to induce platelet aggregation when compared with the absence of a diuretic. However, chlorthalidone was significantly more effective than bendroflumethiazide in reducing epinephrine-mediated platelet aggregation. Chlorthalidone also induced marked changes in the number of gene transcripts for two proteins that mediate angiogenesis and vascular permeability, vascular endothelial growth factor C and transforming growth factor-␤3; chlorthalidone and bendroflumethiazide had contrasting effects on the expression of vascular endothelial growth factor C. Chlorthalidone and bendroflumethiazide reduced vascular permeability to albumin, but only chlorthalidone increased angiogenesis. Thiazides and thiazide-like diuretics can comparably reduce blood pressure, but the drugs in this class are not all alike. It can be suggested from our findings that thiazide and thiazide-like diuretics vary in their pleiotropic effects on platelets and in the vasculature, and these differences could explain the contrasting ability of these drugs to reduce cardiovascular morbidity despite comparable reduction in blood pressure. (Hypertension. 2010;56:463-470.)

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Protective Action of Indapamide, a Thiazide-Like Diuretic, on Ischemia-Induced Injury and Barrier Dysfunction in Mouse Brain Microvascular Endothelial Cells

Cited by 18 publications

References 15 publications

Tissue Plasminogen Activator Enhances the Hypoxia/reoxygenation-induced Impairment of the Blood–brain Barrier in a Primary Culture of Rat Brain Endothelial Cells

Tissue Plasminogen Activator Enhances the Hypoxia/reoxygenation-induced Impairment of the Blood–brain Barrier in a Primary Culture of Rat Brain Endothelial Cells

Diuretics with Carbonic Anhydrase Inhibitory Activity: Toward Novel Applications for Sulfonamide Drugs

Chlorthalidone Decreases Platelet Aggregation and Vascular Permeability and Promotes Angiogenesis

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