Reaction Process: PathBank:SMP0063777

Nitric oxide

NO (29.998)

The biologically active molecule nitric oxide (NO) is a simple, membrane-permeable gas with unique chemistry. It is formed by the conversion of L-arginine to L-citrulline, with the release of NO. The enzymatic oxidation of L-arginine to L-citrulline takes place in the presence of oxygen and NADPH using flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), heme, thiol, and tetrahydrobiopterin as cofactors. The enzyme responsible for the generation of NO is nitric oxide synthase (E.C. 1.7.99.7; NOS). Three NOS isoforms have been described and shown to be encoded on three distinct genes: neuronal NOS (nNOS, NOS type I), inducible NOS (NOS type II), and endothelial NOS (eNOS, NOS type III). Two of them are constitutively expressed and dependent on the presence of calcium ions and calmodulin to function (nNOS and eNOS), while iNOS is considered non-constitutive and calcium-independent. However, experience has shown that constitutive expression of nNOS and eNOS is not as rigid as previously thought (i.e. either present or absent), but can be dynamically controlled during development and in response to injury. Functionally, NO may act as a hormone, neurotransmitter, paracrine messenger, mediator, cytoprotective molecule, and cytotoxic molecule. NO has multiple cellular molecular targets. It influences the activity of transcription factors, modulates upstream signaling cascades, mRNA stability and translation, and processes the primary gene products. In the brain, many processes are linked to NO. NO activates its receptor, soluble guanylate cyclase by binding to it. The stimulation of this enzyme leads to increased synthesis of the second messenger, cGMP, which in turn activates cGMP-dependent kinases in target cells. NO exerts a strong influence on glutamatergic neurotransmission by directly interacting with the N-methyl-D-aspartate (NMDA) receptor. Neuronal NOS is connected to NMDA receptors (see below) and sharply increases NO production following activation of this receptor. Thus, the level of endogenously produced NO around NMDA synapses reflects the activity of glutamate-mediated neurotransmission. However, there is recent evidence showing that non-NMDA glutamate receptors (i.e. AMPA and type I metabotropic receptors) also contribute to NO generation. Besides its influence on glutamate, NO is known to have effects on the storage, uptake and/or release of most other neurotransmitters in the CNS (acetylcholine, dopamine, noradrenaline, GABA, taurine, and glycine) as well as of certain neuropeptides. Finally, since NO is a highly diffusible molecule, it may reach extrasynaptic receptors at target cell membranes that are some distance away from the place of NO synthesis. NO is thus capable of mediating both synaptic and nonsynaptic communication processes. NO is a potent vasodilator (a major endogenous regulator of vascular tone), and an important endothelium-dependent relaxing factor. NO is synthesized by NO synthases (NOS) and NOS are inhibited by asymmetrical dimethylarginine (ADMA). ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) and excreted in the kidneys. Lower ADMA levels in pregnant women compared to non-pregnant controls suggest that ADMA has a role in vascular dilatation and blood pressure changes. Several studies show an increase in ADMA levels in pregnancies complicated with preeclampsia. Elevated ADMA levels in preeclampsia are seen before clinical symptoms have developed; these findings suggest that ADMA has a role in the pathogenesis of preeclampsia. In some pulmonary hypertensive states such as ARDS, the production of endogenous NO may be impaired. Nitric oxide inhalation selectively dilates the pulmonary circulation. Significant systemic vasodilation does not occur because NO is inactivated by rapidly binding to hemoglobin. In an injured lung with pulmonary hypertension, inhaled NO produces local vasodilation of well-ventilated lung units and may "steal" blood flow away from unventil... D002317 - Cardiovascular Agents > D014665 - Vasodilator Agents > D045462 - Endothelium-Dependent Relaxing Factors D019141 - Respiratory System Agents > D018927 - Anti-Asthmatic Agents > D001993 - Bronchodilator Agents D018373 - Peripheral Nervous System Agents > D001337 - Autonomic Agents D018377 - Neurotransmitter Agents > D064426 - Gasotransmitters D000975 - Antioxidants > D016166 - Free Radical Scavengers D020011 - Protective Agents > D000975 - Antioxidants R - Respiratory system

Nitroglycerin

C3H5N3O9 (227.0026)

Nitroglycerin is only found in individuals that have used or taken this drug. It is a volatile vasodilator which relieves angina pectoris by stimulating guanylate cyclase and lowering cytosolic calcium. [PubChem]Similar to other nitrites and organic nitrates, nitroglycerin is converted to nitric oxide (NO), an active intermediate compound which activates the enzyme guanylate cyclase. This stimulates the synthesis of cyclic guanosine 3,5-monophosphate (cGMP) which then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber. The subsequent release of calcium ions results in the relaxation of the smooth muscle cells and vasodilation. C - Cardiovascular system > C05 - Vasoprotectives > C05A - Agents for treatment of hemorrhoids and anal fissures for topical use > C05AE - Muscle relaxants C - Cardiovascular system > C01 - Cardiac therapy > C01D - Vasodilators used in cardiac diseases > C01DA - Organic nitrates COVID info from clinicaltrial, clinicaltrials, clinical trial, clinical trials C78274 - Agent Affecting Cardiovascular System > C29707 - Vasodilating Agent D002317 - Cardiovascular Agents > D014665 - Vasodilator Agents D053834 - Explosive Agents Corona-virus Coronavirus SARS-CoV-2 COVID-19 SARS-CoV COVID19 SARS2 SARS

1,2-Dinitroglycerin

C3H6N2O7 (182.0175)

D002317 - Cardiovascular Agents > D014665 - Vasodilator Agents

Nitrite Ion

NO2- (45.9929)