Polyamine synthesis from l-ornithine is essential for Leishmania growth. We have investigated the dependence of Leishmania infection on arginase, which generates l-ornithine, in macrophages from BALB/c, C57BL/6, and nitric oxide synthase II (NOS II)-deficient mouse strains. We have found that N(omega)-hydroxy-l-arginine (LOHA), a physiological inhibitor of arginase, controls cellular infection ...

Tetrahydrobiopterin (BH(4)) is an essential cofactor for nitric oxide synthases (NOS). This study investigated the effect of increasing BH(4) levels on hypoxia-induced pulmonary vasoconstriction (HPV). Sprague Dawley rats and hph-1 (BH(4) deficient) mice were given BH(4) before and during HPV in an isolated perfused lung preparation. BH(4) inhibited HPV in a concentration-dependent manner and i...

Chronic tissue ischemia due to defective vascular perfusion is a hallmark feature of peripheral artery disease for which minimal therapeutic options exist. We have reported that sodium nitrite therapy exerts cytoprotective effects against acute ischemia/reperfusion injury in both heart and liver, consistent with the model of bioactive NO formation from nitrite during ischemic stress. Here, we t...

The mechanisms underlying cognitive and neurobehavioral abnormalities associated with childhood exposure to manganese (Mn) are not well understood but may be influenced by neuroinflammatory activation of microglia and astrocytes that results in nitrosative stress due to expression of inducible nitric oxide synthase (iNOS/NOS2). We therefore postulated that gene deletion of NOS2 would protect ag...

Nitrite, a physiological nitric oxide (NO) storage form and an alternative way for NO generation, affects numerous biological processes through NO-dependent and independent pathways, including the S-nitrosylation of thiol-containing proteins. Mechanisms underlying these phenomena are not fully understood. The purpose of this study was to analyse in the rat heart (as prototype of mammalian heart...

Nitric oxide (NO), a diffusible gas, is produced in the central nervous system, including the spinal cord dorsal horn and the trigeminal nucleus, the first central areas processing nociceptive information from periphery. In the spinal cord, it has been demonstrated that NO acts as pronociceptive or antinociceptive mediators, apparently in a concentration-dependent manner. However, the central r...

OBJECTIVE Aspirin is known to exert cytoprotection by presently unidentified mechanisms. This study investigates the involvement of nitric oxide (NO) in antioxidant cellular protection induced by aspirin. METHODS AND RESULTS A 24-hour incubation with hydrogen peroxide markedly reduced viability of cultured endothelial cells. Preincubation with aspirin (3 to 30 micromol/L) protected endothelia...

OBJECTIVE To quantify structural and functional characteristics of the caudal artery from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats with particular reference to endothelium-derived hyperpolarizing factor (EDHF). METHODS AND RESULTS Ultrastructural studies showed that the number of myoendothelial gap junctions, smooth muscle cell (SMC) layers, and medial cross-s...

Carbon dioxide (CO2) is involved in plant growth as well as plant responses to abiotic stresses; however, it remains unclear whether CO2 is involved in the response of rice (Oryza sativa) to aluminum (Al) toxicity. In the current study, we discovered that elevated CO2 (600 μL·L-1) significantly alleviated Al-induced inhibition of root elongation that occurred in ambient CO2 (400 μL·L-1). This p...

Tetrahydrobiopterin (BH4) acts as an essential cofactor for the enzymatic activity of nitric oxide (NO) synthases. Biosynthesis of the cofactor BH4 starts from GTP and requires 3 enzymatic steps, which include GTP cyclohydrolase I (GCH I) catalysis of the first and rate-limiting step. In this study we examined the effects of cGMP on GCH I activity in human umbilical vein endothelial cells under...