In vivo demonstration of glomerular PGE2 responses to physiological manipulations and experimental agents

Experiments were carried out in rats to determine whether prostaglandin E2 (PGE2) synthesized in vivo by individual glomeruli could be measured in fluid obtained from early proximal tubule convolutions. A newly developed nonradioactive enzyme-linked immunoassay for PGE2, capable of measuring 0.1- to 0.25-pg quantities, made this approach feasible. In salt-deprived rats, recollection micropuncture samples were obtained from the earliest proximal convolution [tubular fluid-to-plasma insulin ratio (TF/PIn) 1.13] for measurement of PGE2, and then single-nephron glomerular filtration rate (SNGFR). PGE2 was also measured in serum ultrafiltrate, and theoretical maximum "filtered" PGE2 was calculated for each nephron. This was compared with the measured PGE2 from the same nephron. Indomethacin was then given to inhibit cyclooxygenase. We found that measured PGE2 in early proximal fluid (TF) was higher than could be attributed to glomerular filtration. Indomethacin markedly decreased measured PGE2 in early TF. Administration of probenecid, to block tubular transport of PGE2, did not alter the observations. In chronically salt-loaded rats early TF PGE2 was significantly less compared with the salt-deprived rats. Intrarenal infusion of a nonpressor dose of angiotensin II (ANG II) doubled PGE2 appearance in early TF samples. We conclude from these observations that PGE2 in early TF is derived in part from the glomerulus. In the intact rat, glomerular PGE2 synthesis is higher after salt deprivation than after salt loading, inhibited by indomethacin, and stimulated by ANG II. This new approach will allow evaluation of the role of in vivo glomerular PGE2 production in various pathophysiological conditions.