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

Abstract

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 PGD2, PGE 2, PGF2α, PGI2, and TXA2, respectively. Moreover, EP receptors are classified into four subtypes, the EP1, EP2, EP3 and EP4receptors. 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) PGE2 plays a cardioprotective role against the ischemic injury via both the EP3 and EP4, and also participates in acute thromboembolism via the EP3; and 3) both PGF2α and TXA2, which have been produced during systemic inflammation, are responsible for tachycardia.