Vascular endothelium: Vasoactive mediators

Vanhoutte, Paul M.; Mombouli, Jean-Vivien

doi:10.1016/s0033-0620(96)80003-x

Cited by 131 publications

(77 citation statements)

References 65 publications

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“…Endothelial cells express H 1 R (28) and regulate vascular tone, BBB permeability, and migration and extravasation of leukocytes into tissues (39,40). Because H 1 R is important for both Bphs and EAE, and because both Bphs and EAE involve some or all of these physiological processes, we asked whether endothelial H 1 R signaling could similarly affect EAE or Bphs susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Endothelial histamine H ₁ receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis

Lu¹,

Diehl²,

Noubade³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Disruption of the blood-brain barrier (BBB) underlies the development of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis. Environmental factors, such as Bordetella pertussis, are thought to sensitize central endothelium to biogenic amines like histamine, thereby leading to increased BBB permeability. B. pertussis-induced histamine sensitization (Bphs) T he blood-brain barrier (BBB) involves endothelial cells that line the blood vessels of the central nervous system (CNS) and the tight junction protein complexes between these endothelial cells. The BBB thereby acts as a physical and metabolic barrier by separating the vasculature from the parenchyma of the CNS (1). Breakdown of the BBB is associated with the onset and pathogenesis of multiple sclerosis (MS), a degenerative, demyelinating, inflammatory disease of the CNS (2). In MS and its autoimmune model, experimental autoimmune encephalomyelitis (EAE), activated T cells cross the BBB into the perivascular space of the CNS, causing damage to neurons (2). Surveillance of the CNS by T cells does occur (3), but the paucity of leukocytes found in the CNS under noninflammatory conditions suggests that extravasation of cells across the BBB is tightly regulated. Therefore, identifying factors that modulate BBB permeability may be of therapeutical value in treating inflammatory demyelinating diseases of the CNS.Bordetella pertussis-induced hypersensitivity to histamine (Bphs/ Bphs) is a genetically controlled intermediate phenotype associated with susceptibility to EAE (4). Bphs is a state wherein mice are rendered highly susceptible to histamine after a preceding injection of B. pertussis toxin (PTX) (5). Bphs-susceptible strains of mice die within 30 min after histamine challenge, presumably attributable to hypotensive and hypovolemic shock. The cells targeted during Bphs are not known. Histamine has also been implicated in the pathophysiology of MS and EAE. Increased tissue levels of histamine correlate with the onset of EAE (6-8). Mast cells, the major source of histamine (9), are present in MS lesions (10-12), and evidence of mast cell activation is found in the cerebrospinal fluid (CSF) of patients who have MS (13). In mice, mast cells (14) and their activation (15) are required for early EAE onset and maximal disease severity.The effects of histamine are mediated by four surface histamine receptors: H 1 R, H 2 R, H 3 R, and H 4 R (16). H 1 R protein and mRNA are highly expressed in MS lesions (17), and H 1 antihistamines reduce EAE in mice and rats (17,18). In patients with MS, the use of sedating H 1 antihistamines is correlated with decreased disease incidence and amelioration of symptoms (19,20). Our laboratory has shown that susceptibility to Bphs and EAE requires expression of Hrh1, the gene encoding H 1 R (21).Expression of H 1 R on T cells is required for their full encephalitogenic potential (22), but the contribution of H 1 R signaling in other cell types to the pathogenesis of EAE has not been formally addressed. In this study, w...

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Section: Discussionmentioning

confidence: 99%

Endothelial histamine H ₁ receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis

Lu¹,

Diehl²,

Noubade³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…On the other hand, telmisartan clearly improved %FMD, a parameter of vascular endothelium-dependent dilation, while amlodipine showed no effect on %FMD. The vascular endothelium releases various vasoactive substances that exhibit a vasoprotective effect (9,10). Considering that endothelial damage is known to acti- vate smooth muscle cells and cause intimal hypertrophy leading to arteriosclerosis (11), the effect of telmisartan on the intima is very important.…”

Section: Discussionmentioning

confidence: 99%

Renal and Vascular Protective Effects of Telmisartan in Patients with Essential Hypertension

et al. 2006

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“…Similar antibody inhibition patterns were observed when using microsomes from the kidneys of control rats (not shown), thus confirming that the salt-dependent changes in epoxygenase activity result mostly from increases in P-450 2C23 protein concentrations and that these changes are not accompanied by major P-450 2C isoform redistributions. Based on endothelial cell synthesis and release (38), EET-mediated relaxation of preconstricted arteries (39) and G protein-mediated EET opening of vascular smooth cell Ca 2+ -activated K + channels (40,41), the EETs -11,12-EET in particular -were identified as endothelium-derived hyperpolarizing factors (EDHF) (40)(41)(42). These studies, with their potential for providing a molecular understanding of EET vasoactivity, are contributing to the integration of EET ion transport and vasoactive properties into a coherent mechanistic description amenable to experimental analysis.…”

Section: Figurementioning

confidence: 99%

The kidney cytochrome P-450 2C23 arachidonic acid epoxygenase is upregulated during dietary salt loading

Holla¹,

Makita²,

et al. 1999

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Excess dietary salt intake induces the activity of the kidney arachidonate epoxygenase and markedly increases the urinary excretion of its metabolites. The epoxyeicosatrienoic acids, products of the kidney P-450 arachidonate epoxygenase, inhibit distal nephron Na + reabsorption. Nucleic acid hybridization studies demonstrated the expression of P-450s 2C23, 2C24, and 2C11 as the predominant kidney 2C isoforms and the lack of significant dietary salt-dependent transcriptional regulation of these proteins. Recombinant P-450s 2C11, 2C23, and 2C24 catalyze arachidonate metabolism to mixtures of epoxy-and monohydroxylated acids. Whereas the arachidonate 11,12-olefin was the preferred target for epoxidation by P-450 2C23 (57% of total products), P-450s 2C11 and 2C24 epoxidized the 11,12-olefins and 14,15-olefins with nearly equal efficiency. Stereochemical comparisons demonstrated that the regiochemical and enantiofacial selectivity of P-450 2C23 matched that of the kidney microsomal epoxygenase and that excess dietary salt does not alter the regiochemical or stereochemical selectivity of the kidney arachidonate epoxygenase. Inhibition and immunoelectrophoresis experiments using antibodies raised against recombinant P-450s 2C11 and 2C23 demonstrated that P-450 2C23 is the major 2C arachidonic acid epoxygenase in the rat kidney and the renal P-450 isoform regulated by excess dietary salt intake.

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Vascular endothelium: Vasoactive mediators

Cited by 131 publications

References 65 publications

Endothelial histamine H ₁ receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis

Endothelial histamine H ₁ receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis

Renal and Vascular Protective Effects of Telmisartan in Patients with Essential Hypertension

The kidney cytochrome P-450 2C23 arachidonic acid epoxygenase is upregulated during dietary salt loading

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Vascular endothelium: Vasoactive mediators

Cited by 131 publications

References 65 publications

Endothelial histamine H 1 receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis

Endothelial histamine H 1 receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis

Renal and Vascular Protective Effects of Telmisartan in Patients with Essential Hypertension

The kidney cytochrome P-450 2C23 arachidonic acid epoxygenase is upregulated during dietary salt loading

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Endothelial histamine H ₁ receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis

Endothelial histamine H ₁ receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis