Abstract

Tętnicze nadciśnienie płucne jest postępującą chorobą, prowadzącą do niewydolności prawej komory serca i przedwczesnej śmierci. Charakteryzuje się podwyższonym ciśnieniem w tętnicy płucnej, zwiększeniem oporu naczyniowego, przebudową naczyń płucnych oraz dysfunkcją śródbłonka. Patomechanizm tej choroby jest wciąż nieznany. Sugeruje się, że dysfunkcja śródbłonka zaburza równowagę między czynnikami wazodylatacyjnymi a wazokonstrykcyjnymi, w tym np. serotoniną (5-HT). Pierwotnie teorię serotoninową tętniczego nadciśnienia płucnego powiązano z przyjmowaniem leków anoreksygennych, pochodnych fenfluraminy, hamujących wychwyt zwrotny 5-HT. Obecnie potwierdzono zaangażowanie wszystkich składowych układu serotoninergicznego w krążeniu płucnym w tym patomechanizm. W komórkach śródbłonka tętnicy płucnej, hydroksylaza tryptofanu 1 katalizuje reakcję syntezy serotoniny z tryptofanu. 5-HT kurczy naczynia płucne przez pobudzenie receptorów serotoninowych, głównie 5-HT1B i 5-HT2A, a także jest transportowana przez transporter serotoniny (SERT) do wnętrza komórki mięśni gładkich tętnicy płucnej, a następnie działając przez kinazę Rho (ROCK) lub reaktywne formy tlenu powoduje skurcz naczyń i/lub wzrost aktywacji czynników transkrypcyjnych i proliferację. Potwierdzono interakcję między receptorem 5-HT1B i SERT w modulowaniu skurczu naczyń płucnych i ich proliferacji. W pracy omówiono dowody wpływu 5-HT na rozwój tętniczego nadciśnienia płucnego i możliwe cele terapeutyczne w obrębie układu serotoninergicznego.

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