The present study was designed to evaluate, at the microvascular level, the ability of prostaglandins E2 (PGE) and I2 (PGI2) to counteract the afferent vasoconstrictor effects of angiotensin II (ANG II) and norepinephrine (NE). The renal microvasculature of rats pretreated with captopril and indomethacin was studied directly by use of the in vitro blood-perfused juxtamedullary nephron technique combined with videomicroscopy. Afferent arterioles averaged 22-7 ± 0.6 μm ID (n = 59) under control conditions. Topical administration of PGE2 revealed a concentration-dependent afferent vasoconstriction, whereas PGI2 (10-7 to 10 -5 M) failed to significantly alter afferent arteriolar diameter. Afferent arterioles constricted during exposure to either 10-9 M ANG II (-15 ± 3%, n = 13) or 10-7 M NE (-19 ± 3%, n = 13). Addition of PGE2 (10-6 M) to the bathing solution enhanced the vasoconstrictor influences of ANG II and NE by an additional 18 ± 6 and 13 ± 4%, respectively. In contrast, while 10-6 M PGI2 had no effect on ANG II-induced afferent vasoconstriction, it did produce a 30% attenuation of NE-induced constriction. Furthermore, pretreatment of the tissue with 10-6 M PGI2 prevented development of NE-induced afferent vasoconstriction. Thus, although local tissue prostanoid concentrations are unknown, it appears that low micromolar concentrations of PGE2 elicit an afferent arteriolar constriction that can accentuate the vascular actions of ANG II and NE on rat juxtamedullary afferent arterioles. In contrast, PGI2 can counteract the vasoconstrictor response to NE, but not ANG II, in this experimental setting.