( 1 ) NO : ( nitric oxide NO ) NO 2 NO 2. NO O - 2 ( OONO - ) OH NO 2 苷 酶 27 Furchgott Zawadzki 28 ( endothelium-derived relaxing factor, EDRF ) 1987 Palmer 29 EDRF NO superoxide anion EDRF NO superoxide dismutase EDRF NO EDRF NO Palmer 15 N L-arginine NO L-arginine guanidine nitrogen L-citrulline EDRF ( NO ) guanylate cyclase 30,31 28
( 2 ) NO : 32 NO ( L-Arg )-NO L-Arg NO 酶 ( NOS ) NADPH L-Arg -L-Arg O 2 NO L- NO - NO 2 ( NO 3 ) ( NO - 2 ) NO 3 NOS L-Arg NO L- NOS ( nnos ) NOS ( cnos ) NOS 酶 / NADPH NO 酶 NOS ( inos ) 酶 / 酶 LPS 酶酶 NADPH / 酶 NO 29
( 3 ) NO : 32 NO 苷酶 3-5 苷 cgmp NO NO NO NO - 苷 酶 苷酶 酶 cgmp cgmp 酶 C Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca 2+ NO ( 4 ) NO : 酶 ( prostaglands, PGs ) 酶 COX-1 COX-2 酶 COX-2 COX-1 酶 COX-1 COX-2 ( PGE 2 PGI 2 ) 酶 iron-heme center 30
酶 Salvemini 33 RAW264.7 PGE 2 PGE 2 酶 酶 ( ) PGE 2 Salvemini PGI 2 酶 31
( thrombus ) 34,35 ( 1 ) fibrin ( 2 ) 1 platelet adhesion 2 platelet aggregation 3 thrombus formation 1 2 prostacyclin 3 lipoxygenase collagen glycoprotein von Willebrand factor vwf fibrinogen ADP ADP, Epinephrine, thrombin 32
adenylate cyclase c-amp c-amp dense granule phospholipase A 2 酶 ( arachidonic acid ) arachidonic acid synthetase 酶 thromboxane A 2 TXA 2 TXA 2 phospholipase C phosphatidylinositol 4 5-biphosphate inositol-1 4 5-biphosphate IP 3 1 2-diacylglycerol DAG IP 3 DAG protein kinase ADP, thrombin ADP -granule thrombospondin Tetramethylpyrazine phosphoinositide breakdown TXA 2 GP ΙΙb / ΙΙΙa complex 36 Prehispanolone PAF receptor 37 E PMC cyclooxygenase 38,39 Landolfi et al. 40 flavone, chrysin, apigenin phloretin cyclooxygenase 33
41 : ( spontaneously hypertensive rats, SHR ) 1963 Okamoto Wistar-Kyoto ( WKY ) 50 mmhg SHR SHR WKY SHR matrix basement SHR passive tensile stress SHR SHR SHR 90 % Dr. Page 41 34
( chemical ) ( reactivity of vessels ) ( volume ) ( vessel caliber ) ( viscosity ) ( cardiac output ) ( neural ) ( elasticity ) Dr. Frohlich 41 Dr. Page ( renopressor system ) 35
Dr.Page Dr.Frohlich 36
42 23 % superoxide H 2 O 2 hydroxyl radical : hydroxyl radical superoxide dimutase ( SOD ) catalase peroxidase superoxide Superoxide superoxide superoxide NO peroxynitrile H 2 O 2 SOD O 2 NO peroxynitrile Superoxide nicotinamide adenosine dinucleotide dehydrogenase ( NADH ) ubiquinone Q-cytochrome b complex superoxide manganesium SOD H 2 O 2 NO cytochrome oxidase succinate- NADPH-cytochrome c reductase superoxide superoxide NADPH cyclooxygenase xanthine oxidease H 4 B NOS superoxide SOD 37
: SOD SOD SHR 38