NO Activity and Rho Kinase Activity

摘要: General Considerations on Nitric Oxide Purpose and Rationale The endothelium releases a labile, diffusible, vasorelaxing substance that has been termed endotheliumderived relaxing factor (EDRF) (Furchgott Zawadzki 1980). oxide release accounts for the biological activity of endothelium-derived (Palmer et al. 1987; Vanhoutte 1999). plays role in wide range physiological processes including regulation blood flow arterial pressure via endothelium-dependent relaxation vessels (Rees 1989; Moncada 1991; Umans Levi 1995; Huraux 1999; McIntyre Zanzinger Hropot 2003), ischemia/reperfusion injury (Gao 2002; Schulz 2004), peripheral nitrergic transmission at smooth muscle (Rand Li 1995), intracellular communication CNS with activation guanylyl cyclase target neurons (Southam Garthwaite 1993), experimental stroke (Willmot 2005), learning memory (Susswein neurogenic inflammation (Kajekar leukocyte recruitment (Hickey 2001), macrophage defense mechanisms following exposure to bacterial products (Forstermann 1992; Forstermann Kleinert Knowles 1994). Fiorucci (2002) discussed effects nitric oxide-releasing NSAIDs. NO-donor drugs, such as sodium nitrite, nitroprusside, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), 3-morpholino-sydnonimine (SIN-1), are used vasodilators (Schror Megson 2000). N-Nitro-L-arginine was described an antagonist dilator responses by inhibiting (Moore 1990; Lamontagne 1991). Ribero (1992) proposed inhibition synthesis long-term treatment rats nitroL-arginine new model hypertension. Excessive production NO damages DNA activates poly(ADP-ribose)polymerase (PARP) (Pieper In cases massive production, enter PARP-suicide pathway. DNAvia two major pathways: first involves nitrosation primary or secondary amines nucleic acid bases, whereas second combination superoxide form peroxynitrite (Szabo 1996, Szabo 1997). most likely reactive oxidant intermediate responsible breakage is peroxynitrous which rapidly oxidizes sulfhydryl groups also nitrates hydroxylates aromatic compounds tyrosine, tryptophan, guanosine (Halliwell Downstream damage follows excessive results significant leads rapid energy depletion cell death (Feihl 2001). Davis (2001) reviewed non-30,50-cyclic guanosine-monophosphate-mediated modifications proteins, lipids, acids. Andreadis (2003) oxidative nitrosative events asthma.