Abstract—Prostaglandin (PG) E2is an important modulator of the actions of angiotensin (Ang) II. In the present study, we investigated the renal microvascular actions of PGE2and the EP receptor subtypes involved. Ibuprofen potentiated Ang II–induced vasoconstriction in in vitro perfused normal rat kidneys and augmented afferent arteriolar, but not efferent arteriolar, responses in the hydronephrotic rat kidney model. This preglomerular effect of endogenous prostanoids was mimicked by exogenous PGE2, which reversed Ang II–induced afferent arteriolar vasoconstriction at concentrations of 0.1 to 10 nmol/L without affecting the efferent arteriole. The PGE2-induced vasodilation was potentiated by the phosphodiesterase inhibitor Ro 20-1724 and was mimicked by 11-deoxy-PGE1(0.01 to 1 nmol/L). Butaprost, which acts preferentially at EP2receptors, was relatively ineffective. Whereas 0.1 to 10 nmol/L PGE2elicited vasodilation, higher concentrations (1 to 10 μmol/L) restored Ang II–induced afferent arteriolar vasoconstriction. This response was blocked by pertussis toxin (200 μg/mL) and was mimicked by the EP1/EP3agonist sulprostone (1 to 300 nmol/L). Reverse transcription–polymerase chain reaction of individually isolated afferent arterioles revealed the presence of message for EP4and all 3 EP3splice variants (α, β, and γ) but not EP1or EP2. Our findings thus indicate that PGE2elicits both vasodilatory and vasoconstrictor actions on the afferent arteriole. The vasodilation is mediated by EP4receptors coupled to cAMP, presumably via Gαs. The vasoconstriction is mediated by an EP3receptor coupled to Gαiand appears to reflect a functional antagonism of the EP4-induced vasodilation.