Angiotensin II stimulation of prostaglandin E2 and 6-keto-F1α, formation by isolated human glomeruli

Abstract

The intrinsic in vitro production of prostaglandins (PGs) E2, F2 alpha, 6-keto-F1 alpha, and thromboxane B2 (TxB2) and the conversion of exogenous substrate to PGs and TxB2 by isolated human glomeruli was demonstrated, 6-keto-PGF1 alpha was the major product. This was observed under basal conditions and following incubation with exogenous substrate. Indomethacin (Indo; 10(-4 M) inhibited the conversion of arachidonic acid to PGs and the release of [1-14C]-labeled products from human glomeruli by about 80%. The addition of angiotensin II (AII) to the isolated glomeruli produced, under basal conditions, an almost selective stimulation of 6-keto-PGF1 alpha. Following the prelabeling of glomeruli with 1-14C-arachidonic acid, the increase of glomerular PG formation after AII was added was also only significant for 6-keto-PGF1 alpha. When glomeruli were preincubated with large amounts of non-radiolabeled substrate. AII stimulated PGE2 and 6-keto-PGF1 alpha formation significantly. The data demonstrate PG formation in isolated human glomeruli and show an interaction between AII and the prostaglandin system in this tissue. This interrelationship might have physiologic consequences in the regulation of glomerular hemodynamics.

Role of angiotensin II in renal prostaglandin E2 production after furosemide administration.

“…3 ' n Ang n has been shown to stimulate PGE2 and 6-keto-PGF la production by isolated human glomeruli. 13 Therefore, the increase in urinary 6-keto-PGF, a after furosemide administration also might be decreased by captopril, although this was not examined in the present study.…”

“…These observations confirm and extend a previous report by Attallah et al , 6 who suggested that the effect of furosemide on renal PGE2 production is mediated through the action of Ang n. Ang II is reported to stimulate PGE2 synthesis in the kidney," in cultures of renal medullary interstitial cells, 12 and in isolated glomeruli. 13 On the basis of these observations, the observed increment in furosemide-induced renal PGE2 production can be entirely accounted for by the concurrent increase in Ang n . The obliteration of this response by captopril pretreatment provides additional support for this thesis.…”

Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular endothelial cells. Role of the angiotensin type 2 receptor.

“…Plasma renin activity (PRA) was measured as the generation of ANG I/ml/h with RIA using commercially available reagents (Sorin Biomedica, Saluggia, Italy). Kidneys were removed, and glomeruli were isolated by differential sieving with ice-cold Krebs-Ringer buffer as previously described (23). Purity of the preparations was assessed by light microscopy.…”

“…For some experiments, primary culture of rat mesangial cells (MC) were used. MC were isolated from outgrowth of isolated glomeruli obtained from Sprague-Dawley rats by differential sieving as previously described (23). MC stained positive for the Thy-1 antigen, but failed to bind the anti-Factor VIII antibody.…”

Prostaglandin and Thromboxane Formation in Glomeruli from Rats with Reduced Renal Mass

“…Details of oursystem have been previously described [16]. Similar amounts (200-250 pg of glomerular protein) and almost identical amounts (1,027±9 glomeruli) of glomeruli from control (C) and RRM rats were always incubated in parallel.…”