endothelium-derived relaxing factor endothelium-derived relaxing factor the endothelium-derived relaxing factor (edrf) is a strong vasodilator produced by cardiac endothelial cells in response to stress signals such as high levels of adp accumulation or hypoxia. robert f. furchgott is widely recognised for this discovery, even going so far as to be a co-recipient of the 1998 nobel prize in medicine with his colleagues louis j. ignarro and ferid murad. nitric oxide (no) is a key component in any edrf as these compounds either include no or are structurally in the form of no. nitric oxide (no), the principal edrf physiological functions and production anatomical cross section of an artery: the "intima" is composed of endothelial cells edrf serves various functions, of which the most common and topical are vasodilation and the prevention of platelet adhesion. edrf also plays a role in the production of cyclic gmp. edrf is produced from l-arginine by an enzyme (endothelial nitric oxide synthase) that is dependant on calcium-calmodulin and nadph - this occurs in the cardiac endothelium. edrf then diffuses to the smooth muscle in vascular tissue (vessels may be large or small), here it enacts endogenous vasodilation. moreover it serves the function of preventing sympathetic vasoconstriction - when the sympathetic nervous system, reacting to a situation perceived as dangerous, attempts to raise blood pressure through vasoconstriction. the no compound is also capable of reducing clotting in the blood stream due to its ability to prevent platelet adhesion and aggregation. related pathology atherosclerosis and hypertension are grave contributors in the group of pathological conditions under the umbrella of cardiovascular disease. among these conditions is also the disfunction of the endothelium, which given its properties of vasodilation when functional, can cause excessive vasoconstriction, thus leading back to hypertension. another effect of this particular disfunction may also be excessive platelet adhesion, signifying a significant increase in blood clots, thus the promotion of a prothrombotic state. nitric oxide signaling modulatorsforms nitroxyl anion (no−; oxonitrate(1-), hyponitrite anion) nitric oxide (no⋅; nitrogen monoxide) nitrosonium (no+; nitrosyl cation) targetssgc activators/stimulators: ataciguat bay 41-2272 bay 41-8543 bay 60-4552 bi-703704 cinaciguat (bay 58-2667) gsk-2181236a praliciguat riociguat vericiguat inhibitors: odq no donors(prodrugs) nitrates: diethylene glycol dinitrate (degdn) erythritol tetranitrate (etn) ethylene glycol dinitrate (egdn; nitroglycol) isosorbide mononitrate (ismn) isosorbide dinitrate (isdn) itramin tosilate mannitol hexanitrate naproxcinod (nitronaproxen; azd-3582, hct-3012) ncx-466 ncx-2216 ncx-4016 ncx 4040 ncx-4215 nicorandil nipradilol (k-351) nitrate (no−3) nitroatorvastatin (ncx-6560) nitroflurbiprofen (hct-1026) nitrofluvastatin nitroglycerin (glyceryl trinitrate (gtn)) nitropravastatin (ncx-6550) pentaerithrityl tetranitrate (petn) propatylnitrate propylene glycol dinitrate (pgdn) sodium trioxodinitrate (angeli's salt) tenitramine trolnitrate nitroso compounds/nitrites: nitrite (no−2); o-nitroso compounds (alkyl nitrites): amyl nitrite (isoamyl nitrite, isopentyl nitrite) cyclohexyl nitrite ethyl nitrite hexyl nitrite isobutyl nitrite (2-methylpropyl nitrite) isopropyl nitrite methyl nitrite n-butyl nitrite pentyl nitrite tert-butyl nitrite; s-nitroso compounds (thionitrites): la810 s-nitrosoalbumin (snalb) s-nitrosated ar545c s-nitroso-n-acetylcysteine (snac) s-nitroso-n-acetylpenicillamine (snap) s-nitroso-n-valerylpenicillamine (snvp) s-nitrosocaptopril (sno-cap) s-nitrosocysteine (snc, cysno, sno-cys) s-nitrosodiclofenac s-nitrosoglutathione (gsno, snog) sno-t-pa sno-vwf; n-nitroso compounds (e.g., nitrosamines): sin-1a nitrosyl compounds: metal nitrosyl complexes: roussin's black salt roussin's red salt sodium nitroprusside (snp) nonoates (diazeniumdiolates): diethylamine/no (dea/no) diethylenetriamine/no (deta/no) glo/no js-k methylamine hexamethylene methylamine/no (mahma/no) proli/no spermine/no (sper/no) v-pyrro/no heterocyclic compounds: furoxans: furoxan rec15/2739; sydnonimines: feprosidnine linsidomine (sin-1) molsidomine (sin-10) sydnonimine unsorted: cimlanod fk-409 fr144220 fr146881 n-acetyl-n-acetoxy-4-chlorobenzenesulfonamide enzyme(inhibitors)nosnnos 3-bromo-7-nitroindazole 3-chloroindazole 3-chloro-5-nitroindazole 5-nitroindazole 6-nitroindazole 7-nitroindazole a-84643 aminoguanidine (pimagedine) arl-17477 indazole n5-(1-iminoethyl)-l-ornithine (l-nio) nω-methyl-l-arginine (l-nma) nω-propyl-l-arginine (l-npa) nitroarginine (nna, noarg) pentamidine isethionate trim inos 1-amino-2-hydroxyguanidine 2-ethylaminoguanidine 2-iminopiperidine 1400w aeitu aminoguanidine (pimagedine) amt ar-c 102222 byk-191023 canavanine cindunistat (sd-6010) eitu iptu mitu n5-(1-iminoethyl)-l-ornithine (l-nio) n6-(1-iminoethyl)-l-lysine (l-nil) nω-methyl-l-arginine (l-nma) ronopterin (vas-203) trim enos aminoguanidine (pimagedine) n5-(1-iminoethyl)-l-ornithine (l-nio) nω-methyl-l-arginine (l-nma) nitroarginine (nna, noarg) unsorted asymmetric dimethylarginine (adma) ckd-712 guanidinoethyldisulfide (ged) gw-273629 indospicine kd-7040 nitroarginine methyl ester (name) ncx-456 nxn-462 ono-1714 vas-2381 arginase abh nω-hydroxy-l-arginine (noha) chlorogenic acid ginseng epicatechin ornithine norvaline lysine alpha aminoacids camk calmidazolium w-7 others precursors: l-arginine nω-hydroxy-l-arginine (noha) cofactors: nadph fad fmn heme bh4 cam o2 ca2+ indirect/downstream no modulators: ace inhibitors/at-ii receptor antagonists (e.g., captopril, losartan) etb receptor antagonists (e.g., bosentan) l-type calcium channel blockers (e.g., dihydropyridines: nifedipine) nebivolol (beta blocker) pde5 inhibitors (e.g., sildenafil) non-selective pde inhibitors (e.g., caffeine) pde9 inhibitors (e.g., paraxanthine) cgmp preferring pde inhibitors (e.g., sildenafil, paraxanthine, tadalafil) statins (e.g., simvastatin)