A thromboxane prostanoid receptor (TP-R) agonist, U-46,619 enhances tubuloglomerular feedback (TGF). Glomerular expression of TP-R and enhancement of TGF by U-46,619 increase with salt intake. We investigated the hypothesis that 8-Isoprostaglandin F₂ (8-Iso) activates TGF via TP-R. The maximal TGF response in rats was assessed from the fall in proximal stop flow pressure (PSF; an index of glomerular capillary pressure) during loop of Henle (LH) microperfusion of artificial tubular fluid (ATF) at 40 nl/min. Microperfusion of 8-Iso (10^-4M) into the efferent arteriole (EA) enhanced TGF responses by 20±3% (p<0.01). TGF response to 8-Iso was independent of dietary salt (TGF%, LS: 21±5%, NS: 17±4%, HS: 29±8%, ns), unlike the salt dependent effect of U-46, 619 (TGF%, LS: 41±5%; NS: 52±4%; HS: 112±21%). Ifetroban, the TP-R antagonist abolished TGF responses to 8-Iso and U-46,619 at all levels of salt intake. During luminal perfusion of L-NMA, the effect of 8-Iso on TGF was enhanced in NS and HS, but not in LS (LS: 22±6 vs. LS+L-NMA: 28±6%, ns; NS: 18±4 vs. NS+L-NMA: 40±4, p<0.01; HS: 27±3 vs. HS+L-NMA: 65±6, p<0.01). However, U-46,619 did not further increase TGF after L-NMA in all salt groups (LS: 43±7 vs LS+L-NMA: 51±6, ns; NS: 52±7 vs NS+L-NMA: 48±8, ns; HS: 114±21 vs HS+L-NMA: 74±22, ns). In conclusion, activation of TP receptors by U-46,619 and 8-Iso-PGF₂ enhances TGF. In addition, the effect of U-46, 619 was salt dependent, whereas the effect of 8-Iso-PGF₂ was salt independent. However, stimulation of NO by 8-isoprostanes masks its salt sensitive effect on TGF.