2003
DOI: 10.1124/jpet.103.057422
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p38 MAPK Inhibitors Ameliorate Target Organ Damage in Hypertension: Part 1. p38 MAPK-Dependent Endothelial Dysfunction and Hypertension

Abstract: Numerous mediators, believed to play a role in endothelial dysfunction (e.g., neurohormones, cytokines, hypoxia, and stretch), have been shown to activate p38 mitogen-activated protein kinase (MAPK) in a variety of cell types. The purpose of the present study was to examine the regulation of p38 MAPK in endothelium and its role in endothelial dysfunction and salt sensitivity. In cultured human umbilical vein endothelial cells (HUVECs), tumor necrosis factor-␣ and lipopolysaccharide increased phosphorylation of… Show more

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Cited by 59 publications
(54 citation statements)
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“…Consistent with the histological changes observed in the kidney, albuminuria was significantly reduced in the SFD ϩ SB-239063 group. It is noteworthy, that the beneficial effects of p38 MAPK inhibition may have been underestimated in this study in that 80% of SFD ϩ SB-239063 animals survived the protocol compared with only 50% in the SFD control group (similar results as in Part 1 of this study; Ju et al, 2003). Thus we were unable to assess the severe renal dysfunction that is known to accompany morbidity in the SFD control group.…”
Section: Discussioncontrasting
confidence: 47%
See 1 more Smart Citation
“…Consistent with the histological changes observed in the kidney, albuminuria was significantly reduced in the SFD ϩ SB-239063 group. It is noteworthy, that the beneficial effects of p38 MAPK inhibition may have been underestimated in this study in that 80% of SFD ϩ SB-239063 animals survived the protocol compared with only 50% in the SFD control group (similar results as in Part 1 of this study; Ju et al, 2003). Thus we were unable to assess the severe renal dysfunction that is known to accompany morbidity in the SFD control group.…”
Section: Discussioncontrasting
confidence: 47%
“…Part 1 of this study (Ju et al, 2003) illustrates the role of p38 MAPK in endothelial dysfunction associated with a salt/ fat-sensitive model of hypertension and the reversal of this dysfunction after p38 MAPK inhibition. In Part 2 of this study, we examined the role of p38 MAPK inhibition on the renal dysfunction associated with this salt/fat-sensitive model of hypertension.…”
mentioning
confidence: 99%
“…Many studies have associated increased levels of cytokines or high glucose levels in the bloodstream with increased p38 activity and endothelial dysfunction (1)(2)(3)(4). The mechanism controlling endothelial dysfunction is not clearly understood.…”
Section: Fig 9 Mek6e-induced Migration and Actin Reorganization Invmentioning
confidence: 99%
“…However, several pathological conditions such as hypertension and hyperglycemia are accompanied by a dysfunctional endothelium characterized by impaired re-endothelialization. These conditions are associated with elevated levels of cytokines such as tumor necrosis factor and transforming growth factor-␤ as well as enhanced activation of p38 (1)(2)(3)(4)(5). Interestingly, high glucose levels present in diabetic patients have also been shown to induce the activation of p38 (1).…”
mentioning
confidence: 99%
“…Several mechanisms have been proposed for druginduced prolongation of life span in SHRSP: 1) reduction of BP (20,26,27), 2) modulation of inflammation (26,28), 3) prevention of extracellular matrix accumulation (29), 4), inhibition of superoxide production (28), and 5) reduction of platelet aggregation (27). In this study, we examined the dosing-time-dependent effects of Val on BP and IL-1β and IL-6 levels, the markers of inflammation.…”
Section: Discussionmentioning
confidence: 99%