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Nitric oxide synthases produce NO by catalysing a five-electron oxidation of a guanidino nitrogen of L-arginine (L-Arg). Oxidation of L-Arg to L-citrulline occurs via two successive monooxygenation reactions producing N ω-hydroxy-L-arginine (NOHLA) as an intermediate. 2 mol of O 2 and 1.5 mol of NADPH are consumed per mole of NO formed. [3]
Endothelial NOS (eNOS), also known as nitric oxide synthase 3 (NOS3) or constitutive NOS (cNOS), is an enzyme that in humans is encoded by the NOS3 gene located in the 7q35-7q36 region of chromosome 7. [5]
A nitrovasodilator is a pharmaceutical agent that causes vasodilation (widening of blood vessels) by donation of nitric oxide (NO), [1] and is mostly used for the treatment and prevention of angina pectoris. This group of drugs includes nitrates (esters of nitric acid), which are reduced to NO in the body, as well as some other substances.
The importance of developing such drugs was increased when COX-2-specific NSAIDs rofecoxib (Vioxx) and lumiracoxib (Prexige) were removed from major pharmaceutical markets in the mid-2000s due to vascular safety concerns. In addition, traditional NSAIDs increase blood pressure and interfere with the actions of antihypertensive drugs.
Rho-kinase also decreases nitric oxide synthase activity, which reduces nitric oxide concentrations. [3] Lower levels of nitric oxide are present in spastic coronary arteries. [ 4 ] L-type calcium channel expression increases in spastic vascular smooth muscle cells, which could result in excessive calcium influx, and hypercontraction.
The enzyme endothelial nitric oxide synthase produces nitric oxide from arginine in endothelial cells. [9] Argininosuccinate synthetase and argininosuccinate lyase recycle citrulline, a byproduct of nitric oxide production, into arginine. Since nitric oxide is an important signaling molecule, this role of ASS is important to vascular physiology.
Riociguat, sold under the brand name Adempas, is a medication by Bayer that is a stimulator of soluble guanylate cyclase (sGC). It is used to treat two forms of pulmonary hypertension (PH): chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH).
7-Nitroindazole, or 7-NI, is a heterocyclic small molecule containing an indazole ring that has been nitrated at the 7 position. Nitroindazole acts as a selective inhibitor for neuronal nitric oxide synthase, a hemoprotein enzyme that, in neuronal tissue, converts arginine to citrulline and nitric oxide (NO). [1]