In order to exert an appropriate biological effect, the action of the vasoconstrictive hormone angiotensin II (ANG II) is modulated by vasoactive factors such as prostaglandins PGE₂ and PGI₂. The present study investigates whether prostaglandins alter ANG II-mediated increases in cytosolic calcium concentration ([Ca²⁺]_i) in vascular smooth muscle cells (VSMC) isolated from rat renal preglomerular arterioles. [Ca²⁺]_i was assessed using the calcium-sensitive dye fura 2 and a microscope-based photometer system. ANG II (10⁻⁷ M) caused a biphasic, time-dependent [Ca²⁺]_i response: an initial peak increase from 52 ± 7 to 264 ± 25 nM, followed by a sustained plateau of 95 ± 9 nM in cultured VSMC. Coadministration of PGE₂ or PGI₂ or synthetic mimetics caused dose-dependent decreases in the peak [Ca²⁺]_i response to ANG II, with attenuation of 40–50%. This degree of inhibition was even more pronounced in individual freshly isolated preglomerular VSMC. Increasing cAMP levels in cultured VSMC, by using either a cell-permeable analog or inhibiting phosphodiesterase activity, mirrored the antagonistic effects of prostaglandins on ANG II-stimulated increases in [Ca²⁺]_i. Radioimmunoassays demonstrate that ANG II (10⁻⁷ M) stimulates production of PGI₂ and PGE₂; the stable prostacyclin metabolite 6-keto-PGF_{1 α}was released in 10-fold greater concentrations than PGE_2.Indomethacin blockade of prostaglandin production potentiated both the peak (264 to 337 ± 26 nM) and sustained [Ca²⁺]_i responses (95 to 181 ± 22 nM) to ANG II. When prostaglandin analogs were added during indomethacin treatment, the ANG II response was restored to the typical pattern. In conclusion, we demonstrate that modulation of intracellular calcium levels is one mechanism by which prostaglandins can buffer ANG II-mediated constriction in renal preglomerular VSMC. PGI₂ is more potent than PGE₂ in this regard.