Uloge endotelina u kardiovaskularnoj fiziologiji i patofiziologiji od njegovog otkrića do danas su neosporne. U srcu endotelini su značajni za procese razvoja, rasta i remodelovanja kao i za kontrolu kontraktilnosti i ritmičnosti. Srčane endotelne ćelije u endokardu i miokardnim kapilarima predstavljaju glavni izvor endotelina, a kardiomiociti su njihova primarna meta. Endotelin-1 je jedna od najpotentnijih poznatih supstanci sa pozitivnim inotropnim efektom, stoga endotelini imaju ključnu ulogu u srčanoj endotelno-miokardnoj interakciji. Endotelini su familija peptida od 21 amino kiseline koju čine endotelin-1, endotelin-2 i endotelin-3. Ostvaruju svoje efekte aktivacijom endotelinskih receptora, ETA i ETB, koji pripadaju familiji receptora vezanih za G proteine. ETA i ETB receptori su gusto distribuirani na kardiomiocitima, ćelijama provodnog sistema srca, koronarno vaskularnim i endokardno endotelnim ćelijama. U fiziološkim uslovima mesto sinteze endotelina su endotelne ćelije ali u patofiziološkim uslovima i veliki broj neendotelnih ćelija u srcu. Endotelin-1 ima pozitivno hronotropno i inotropno dejstvo. Administracija ET-1 uzrokuje koronarnu vazokonstrikciju, dovodi do ishemije miokarda i letalne ventrikularne aritmije. U akutnom infarktu miokarda ET-1 povećava miokardnu nekrozu i aritmije ali ima povoljan efekat na oporavak srca nakon infarkta u početnoj fazi remodelovanja srca. ET-1 preokreće acidozom indukovan negativan inotropan i luzitropan efekat, bez povećanja intracelularnog kalcijuma. Endotelin može da se suprotstavi aritmogenim efektima kateholamina. Tako, male koncentracije endotelina imaju protektivni efekat na srce. Osnovne indikacije za primenu antagonista endotelina jesu srčana insuficijencija, plućna hipertenzija i rezistentna arterijska hipertenzija. Dobro i pažljivo dizajnirane kliničke studije su potrebne za verifikaciju terapeutskih potencijala novih klasa lekova u kardiovaskularnoj medicini.
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