Physiological involvement of placental endothelin-1 and prostaglandin F_2α in uteroplacental circulatory disturbance in pregnant rats exposed to heat stress

Several studies suggest that heat stress affects placental functions including uteroplacental circulation, subsequently leading to pregnancy failure and birth weight reduction. To clarify the involvement of endothelin and placental prostaglandin (PG) systems in the uteroplacental circulation during heat stress, we examined the effects of i.v. administration of the endothelin receptor antagonist bosentan and the cyclooxygenase inhibitor indomethacin on uteroplacental blood flow and on placental PGE₂ and PGF _2α levels and their 13,14-dyhydro-15-keto-metabolites (PGEM and PGFM, respectively) in heat-exposed or non-heat-exposed pregnant rats. The administration of bosentan or indomethacin did not change uteroplacental blood flow in non-heat-exposed pregnant rats. In contrast, heat reduced uteroplacental blood flow in pregnant rats, but the reduction was reversed by the administration of bosentan or indomethacin before heat exposure. Heat did not change placental PGE₂ or PGEM levels, but in pregnant rats it increased placental PGF_2α, and PGFM levels, which were reversed by bosentan or indomethacin. Our results suggest that the activation of placental endothelin receptor and PGF_2α systems are involved in the uteroplacental circulatory disturbances produced by heat. PGF _2α systems activated by heat may be involved in the vasoconstricting effects of endothelin-A and -B receptors during heat exposure.