Pathophysiological roles of the prostanoids in the cardiovascular system: Studies using mice deficient in prostanoid receptors.

摘要

Prostanoids, consisting of the prostaglandins (PGs) and thromboxanes (TXs), exert various actions through activation of their specific receptors. They include the DP, EP, FP, IP, and TP receptors for PGD(2), PGE(2), PGF(2)alpha, PGI(2), and TXA(2), respectively. Moreover, EP receptors are classified into four subtypes, the EP(1), EP(2), EP(3) and EP(4) receptors. Using mice lacking prostanoid receptors, we intended to clarify in vivo roles of prostanoids under pathophysiological conditions of the cardiovascular system, which include ischemia-induced cardiac injury, pressure overload-induced cardiac hypertrophy, renovascular hypertension, tachycardia during systemic inflammation and thromboembolism. The results demonstrated that 1) PGI(2) plays an important role in attenuating the ischemic injury and the pressure overload-induced hypertrophy of the hearts, and also contributes to the development of renovascular hypertension; 2) PGE(2) plays a cardioprotective role against the ischemic injury via both the EP(3) and EP(4), and also participates in acute thromboembolism via the EP(3); and 3) both PGF(2)alpha and TXA(2), which have been produced during systemic inflammation, are responsible for tachycardia.