OBJECTIVE Continuous administration of nitroglycerin (GTN) causes tolerance and endothelial dysfunction by inducing reactive oxygen species (ROS) production from various enzymatic sources, such as mitochondria, NADPH oxidase, and an uncoupled endothelial nitric oxide synthase (eNOS). In the present study, we tested the effects of type 1 angiotensin (AT(1))-receptor blockade with telmisartan on ...

We assessed the effects of dexamethasone (DEX) on hypoxia-induced dysfunction of the pulmonary endothelium using organ-cultured rabbit intrapulmonary arteries; 3-microM DEX inhibited the 7-day hypoxia (5% oxygen)-induced impairments of endothelial-dependent relaxation, cGMP accumulation, and increase in intracellular Ca(2+) level under substance P-stimulated conditions. Treatment with DEX over ...

In addition to superoxide (O2.-) generation from nitric oxide synthase (NOS) oxygenase domain, a new O2.- generation site has been identified in the reductase domain of inducible NOS (iNOS) and neuronal NOS (nNOS). Cysteine S-glutathionylation in eNOS reductase domain also induces O2.- generation from eNOS reductase domain. However, the characteristics and regulatory mechanism of the O2.- gener...

Letters to the Editor will be published, if suitable, as space permits. They should not exceed 1000 words (typed double-spaced) in length and may be subject to editing or abridgment. To the Editor: In their recently published article in Hypertension, Chiasson and colleagues, 1 in contrast to Ruan et al, 2 demonstrated that binding of Pin1 to endothelial NO synthase (eNOS) facilitates the dephos...

AIMS We investigated the molecular mechanism underlying the role of transient receptor potential vanilloid type 1 (TRPV1), a Ca(2+)-permeable non-selective cation channel, in the activation of endothelial nitric oxide (NO) synthase (eNOS) in endothelial cells (ECs) and mice. METHODS AND RESULTS In ECs, TRPV1 ligands (evodiamine or capsaicin) promoted NO production, eNOS phosphorylation, and t...

eNOS (endothelial nitric oxide synthase) contains a MAPK (mitogen-activated protein kinase)-binding site associated with a major eNOS control element. Purified ERK (extracellular-signal-regulated kinase) phosphorylates eNOS with a stoichiometry of 2-3 phosphates per eNOS monomer. Phosphorylation decreases NO synthesis and cytochrome c reductase activity. Three sites of phosphorylation were dete...

OBJECTIVE This study was to investigate the molecular mechanisms underlying the 27nt-miRNA-mediated regulation of expression of the endothelial nitric oxide synthase (eNOS) gene. METHODS Cell lines overexpressing 27nt-miRNA or its mutant were established by transfecting the miRNA expression vector into the endothelial cells. eNOS mRNA and protein expression were examined by RT-PCR and Western...

The actions of acetylcholine (ACh) on endothelium mainly are mediated through muscarinic receptors, which are members of the G protein-coupled receptor family. In the present study, we show that ACh induces rapid tyrosine phosphorylation and activation of Janus kinase 2 (JAK2) in rat aorta. Upon JAK2 activation, tyrosine phosphorylation of insulin receptor substrate (IRS)-1 is detected. In addi...

Estrogen has been shown to increase endothelium-dependent vasodilation and expression of endothelial nitric oxide (NO) synthase (eNOS); however, the role of estrogen receptors in mediating estrogen effects on endothelial function remains to be elucidated. The purpose of this study was to test the hypothesis that estrogen modulates NO-dependent vasodilation of coronary arteries through its actio...