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1、JournaloftheAmericanCollegeofCardiologyVol.59,No.22,2012?2012bytheAmericanCollegeofCardiologyFoundationISSN0735-1097/$36.00PublishedbyElsevierInc.doi:10.1016/j.jacc.2011.09.086STATE-OF-THE-ARTPAPERCyclicGuanosineMonophosphateSignalingandPhosphodiesterase-5Inhibi
2、torsinCardioprotectionRakeshC.Kukreja,PHD,FadiN.Salloum,PHD,AninditaDas,PHDRichmond,VirginiaCyclicguanosinemonophosphate(cGMP)isanimportantintracellularsecondmessengerthatmediatesmultipletissueandcellularresponses.ThecGMPpathwayisakeyelementinthepathophysiologyo
3、ftheheartanditsmodulationbydrugssuchasphosphodiesterase(PDE)-5inhibitorsandguanylatecyclaseactivatorsmayrepre-sentapromisingtherapeuticapproachforacutemyocardialinfarction,cardiachypertrophy,heartfailure,anddoxorubicincardiotoxicityinpatients.Inaddition,PDE-5inh
4、ibitorsmayprovetobeinnovativetherapeuticagentsforenhancingthechemosensitivityofdoxorubicinwhileprovidingconcurrentcardiacbene?t.(JAmCollCardiol2012;59:1921–7)?2012bytheAmericanCollegeofCardiologyFoundationCyclicguanosinemonophosphate(cGMP)isacriticalofcyclicaden
5、osinemonophosphate(cAMP)and/orcGMPintracellularsecondmessengerregulatingfundamentaltoproducethecorresponding5nucleotide.Currently,21physiologicalprocessesinthemyocardium,fromacutePDEgeneshavebeenclonedandareclassi?edinto11contraction/relaxationtochronicgeneexpre
6、ssion,cellfamiliesaccordingtotheirsequenceofhomology,biochem-growth,andapoptosis.Severalstudieshaveshownthatical,andpharmacologicalproperties(6).ThePDEsvaryincGMPinhibitshypertrophy,reducesischemia-reperfusiontheirsubstratespeci?cityforcAMPandcGMP:PDE-5,(I/R)inj
7、ury,andregulatescontractilefunctionandcardiacPDE-6,andPDE-9arespeci?cforcGMP;PDE-4,remodeling(13).cGMPisgeneratedfromthecytosolicPDE-7,andPDE-8arespeci?cforcAMP;andPDE-1,purinenucleotideguanosinetriphosphatebyguanylylcy-PDE-2,PDE-3,PDE-10,andPDE-11havemixedspec-
8、22lases(GCs)usingMgorMnascofactors.Twoi?cityforcAMP/cGMP(7).PDE-5selectivelyhydrolyzesisoformsofGCsexistinvertebratecellsandtissues:anitriccGMP,anditsinhibitionincr
