nitric oxide

Nitric Oxide

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Nitric Oxide Nitric Oxide (NO) is a soluble gas An important cell signaling molecule with diverse actions on cardiovascular, renal and immune cell function. NO was formerly knows as endothelial-derived relaxing factor (EDRF) that is produced by endothelial cells following activation by agonists (ACh,GABA, or ADENOSINE)

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Biosynthesis Nitric oxide is produced de novo from the precursor amino acid L-arginine L-arginine,, the reaction is catalyzed by the enzyme Nitric Oxide Synthase (NOS) in presence of molecular oxygen. The

products are NO and L-citrulline www.pharmapublications.in

Biosynthesis

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Nitric Oxide Synthase (NOS) Constitutional ±

NOS I (n NOS)

Neuornal

±

NOS III (e NOS)

Endothelial

Inducible ±

NOS II or iNOS

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nNOS (neuronal NOS, NOS I) n NOS is found in the brain, peripheral neurons, some vascular and epithelial smooth muscle and in skeletal muscles. The

produced NO functions as

neurotransmitter and an d neuromodulator neuromodulator..

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iNOS (inducible, NOS II) i NOS is induced by cytokines from different tissues such as macrophages, glial cells, hepatocytes, endothelium, cardiac myocytes and smooth muscles. The

NO produced eradicates infections and

combats tumors (cytotoxicity). www.pharmapublications.in

eNOS (endothelial constitutive, NOS III) It is expressed in tissues such as endothelium pulmonary and renal epithelium, cardiac myocytes and hippocampus. The

produced NO functions as vascular tone

regulator and regulator of blood supply to organs. www.pharmapublications.in

Endothelial NOS

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Mechanism of action of NO:

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Mechanism of action

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Mechanism ofAction Increase in cyclic guanosine monophosphate (cGMP), activates cGMP-dependent protein kinase leading to ±

Opening of K+ channels causing hyperpolarization

±

Inactivation of operated calcium channels causing decrease calcium channels causing decrease in calcium influx

±

The resultant effect is vasodilation or muscle relaxation

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Pharmacological Manipulation of  Nitric Oxide Inhibitors of Nitric Oxide Synthesis Nitric Oxide Donors

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Inhibitors of NOS Enzyme i nhibitors are arginine analogs that bind to the The majority of these inhibitors NOS arginine-binding site. In inflammatory disorders and sepsis, inhibition inhibition of the iNOS isoform is potentially beneficial. However,, administration of nonselective NOS inhibitors leads to However concurrent inhibition of eNOS, which impairs its it s homeostatic homeostatic signaling signali ng and also results in vasoconstriction and potential ischemic damage. xample : xample E 

N-Monomethyl-L-arginin (L-NMMA) N-Monomethyl-L-arginin www.pharmapublications.in

Nitric Oxide Donors Nitroglycerine, nitroprusside, nitrite and nitrates. These

are clinically effective in angina

pectoris as vasodilators and in other cardiac diseases.

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Nitric Oxide Donors

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Thank

You

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