BACKGROUND Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The bioavailability of the potent vasodilator nitric oxide (NO) depends on competition between NO synthase-3 (NOS3) and arginases for their common substrate (L-arginine). We tested the hypothesis whereby tobacco smoking impairs pulmonary endothelial function via upregulation of the arginase pathwa...

Synaptic plasticity directs development of the nervous system and is thought to underlie memory storage in adult animals. A great deal of our current understanding of the role of AMPA receptors in synaptic plasticity comes from studies on developing cortex and cell cultures. In the present study, we instead focus on plasticity in mature neurons in the neocortex of adult animals. We find that th...

Calcineurin (PP2B) has recently been shown to be upregulated in the medullary thick ascending limb (mTAL) during diabetes. The mTAL expresses all three isoforms of nitric oxide synthase (NOS), which are subject to phosphoregulation and represent substrates for PP2B. Therefore, we hypothesized that diabetes induces PP2B-dependent upregulation of NOS activity and NO production in the mTAL. Three ...

It has been known for decades that increased dietary intake of salt (NaCl) shortens the life span of rats in a dose-dependent fashion. This review focuses specifically on the recently described biological effect and consequences of increased salt ingestion on the endothelium through a mechanism that is independent of blood pressure. Changes in salt intake are recognized by endothelial cells in ...

Inhaled nitric oxide (NO) is a highly selective pulmonary vasodilator. It was recently reported that inhaled NO causes peripheral vasodilatation after treatment with a NO synthase (NOS) inhibitor. These findings suggested the possibility that inhibition of endogenous NOS uncovered the systemic vasodilating effect of NO or NO adducts absorbed via the lungs during NO inhalation. To learn whether ...

Nitric oxide (NO) is a gaseous molecule with neurotransmitter properties that is involved in numerous functions in the central nervous system (CNS), the vascular system and also in macrophages. Haplotypes of NOS1 and NOS3 genes have been shown to be associated with different psychiatric disorders such as schizophrenia and bipolar disorder. Therefore, the detection of other characteristics of ni...

Endothelium-mediated vasodilation is specifically enhanced in uterine circulation during pregnancy, and production of nitric oxide (NO) is increased in response to a wide array of agonists. Uterine artery endothelial cells from nonpregnant (NP-UAECs) or pregnant (P-UAECs) ewes maintained in culture still show a pregnancy-enhanced difference in ATP-stimulated endothelial NO synthase (eNOS; offic...

Purpose: Numerous chemotherapeutic agents are cytotoxic through generation of reactive species, and variability in genes related to oxidative stress may influence disease-free survival (DFS). We examined relationships between DFS and variants in NOS3, as well as NQO1, NQO2, and CBR3, among treated and untreated breast cancer patients in a Southwest Oncology Group clinical trial (S8897). Experim...

Studies on the associations between the nitric oxide synthase gene (NOS3) Glu298Asp polymorphism and hypertension status or blood pressure (BP) levels have had inconsistent results. Potential moderating influences of ethnicity, sex, and obesity on the effects of the NOS3 polymorphism have not been examined. We evaluated the influence of these factors on associations between the NOS3 polymorphis...

PURPOSE Epidemiologic studies suggest that several gene variants increase the risk of stroke, and population-based studies help provide further evidence. We identified polymorphisms associated with the prevalence of self-reported stroke in US populations using a representative sample. METHODS Our sample comprised US adults in the Third National Health and Nutrition Examination (NHANES III) DN...