Mechanism of action of NO occurs by
NO is a sho-lived, soluble, free radical gas NO is synthesized de novo from L-arginine, molecular oxygen, and NADPH by the enzyme nitric oxide synthase three isoforms of NOS are present Type I, neuronal NOS (nNOS)- present in Neurons, does not play a significant role in inflammation. Type II, inducible NOS (iNOS)- inducible form, responsible for the production of NO in inflammatory reactions. Type III, endothelial NOS, (eNOS)- synthesized primarily (but not exclusively) in the endothelium impoant actions regulation of neurotransmitter release potent vasodilator killing microbes and tumour cells. Endogenous regulator of leucocyte recruitment antagonism of all stages of platelet activation Mechanism of action NO induces vasodilation by acting on guanylate cyclase Cyclic-GMP activates protein kinase causes reuptake of ca2+ which activates potassium channel fall in ca 2+, myosin light chain kinase cannot phosphorylate myosin no cross bridging relaxation Robbins pathology 9th ed page 49
c-AMP
c-GMP
Intracellular pathway
IP3/DAG
General pathology